Chapter  78:  Best-Case Series for the Use of Immuno-Augmentation Therapy and Naltrexone for the Treatment of Cancer

Overview

This report presents an assessment of patients with cancer treated with either of two complementary and alternative medicine (CAM) therapies, Immuno-Augmentation Therapy (IAT) or low-dose Naltrexone. Some patients report that these treatments have improved their health-related quality of life. Two clinics that treat patients with these therapies were identified by staff at the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health. In selecting patients' records for review, the researchers used criteria developed by the National Cancer Institute for its “best-case series.” These criteria require rigorous and objective evidence of the patient's clinical condition and treatment received. A “best-case series” can provide information on the efficacy of a treatment in the absence of a controlled clinical trial. The researchers judged nine cases in which patients received IAT and three cases in which patients received Naltrexone, to best meet the “best-case series” criteria, and these cases are reported in detail herein. The authors also report on the difficulties identifying “best-case series” for these patients.

Methodology

The project's staff visited the two sites and asked the CAM providers to identify their best cases based on their belief that the patients benefited from the treatment. The staff screened these and additional patient files that were identified from the clinic records, based on the criteria for a best-case series established by the National Cancer Institute.

In a “best-case series,” cases are not selected randomly and are not representative of the “average” or “typical” case. Furthermore, there are no control cases that would facilitate a comparison of patient outcomes with and without the treatment in question. A best-case series relies on assumptions about patient outcomes in the absence of treatment, and consequently requires very rigorous documentation of the patient's clinical status. This information is then used by clinical experts to make judgments about outcomes in similar patients treated with the best available conventional therapy. This is the basis for conclusions regarding the potential efficacy of the treatment in question. Best-case series are useful to help identify therapies that have sufficient promise of efficacy to justify the time and resources necessary for more rigorous study, such as a clinical trial.

For this study, the researchers used criteria developed by the Office of Cancer Complementary and Alternative Medicine (OCCAM), a part of the National Cancer Institute. These criteria require the following:

1. Documentation of the diagnosis of cancer. The patient's cancer should be documented by obtaining tumor tissue and having it examined by a pathologist. The pathologist's report should be included in the case summary.

2. Evaluation of the appropriate antitumor endpoint. The only reliable antitumor endpoint that can be documented in a best-case series is a demonstrable and reproducible reduction of tumor size. Tumor measurements are made before treatment, during treatment, and after treatment is complete. An objective response is considered to be a decrease of at least 50 percent in the area of the tumor (i.e., the cross product of the diameters) with no increase in size of any other lesions.

3. The patient must not be receiving any other treatment for his/her cancer. To document an antitumor effect based upon individual patient histories, the patient must have a documented, measurable tumor just before the CAM modalities are given. While the CAM modalities themselves may have multiple components, they must not be given together with any other cancer treatments.

4. A record of previous anti-cancer treatments.

5. Documentation of sites of the cancer. At least one recurrent or metastatic cancer should be documented histologically. The date at which recurrence or metastatic disease was first noted should be provided.

6. Description of the patient's general medical condition. The age, sex, and any other previous or concurrent illnesses or significant medical conditions should be carefully documented.

7. Description of the treatment administered. The treatment that was felt to result in the antitumor response should be described.

Promising cases were identified, and these patients were contacted to obtain permission for the researchers to abstract their files. After consents were obtained, patients were interviewed by telephone; for deceased patients, their next of kin were interviewed. All data collected from abstraction forms and the interview were summarized on a case report form. The most pertinent clinical data (radiology studies, pathology slides) were identified, and original clinical material was requested from the appropriate institution. If the original clinical material was still available, it was sent to the Southern California Evidence-Based Practice Center (SCEPC).

Several instruments were developed specifically for this project: Cancer Best-Case Series Abstraction Form; Case Report Form; and IAT and Naltrexone Patient Interview Questionnaires. The patient questionnaire includes a Health-Related Quality of Life instrument, the European Organization for Research and the Treatment of Cancer Quality of Life Questionnaire (QLQ-C30).

Findings

For IAT, the researchers reviewed in detail 30 cases (out of 60 promising cases) that had the potential to be included in a best-case series. Of those, nine cases are presented that the researchers consider the most complete or appropriate in terms of the NCI criteria for a best-case series. These cases include the following types of cancer: Hodgkin's lymphoma, non-small-cell carcinoma of the lung, nodular lymphoma (poorly differentiated), peritoneal mesothelioma (two cases), ovarian adenocarcinoma, squamous cell carcinoma of vocal cord (two cases), and adenocarcinoma of the colon.

For naltrexone treatments, three cases of the 21 that the researchers reviewed in depth best met the NCI criteria. These include the following cancers: melanoma, pancreatic cancer, and endometrial adenocarcinoma with a second primary breast adenocarcinoma (single case). These cases represent the best that the authors were able to assemble using the currently accepted NCI best-case method.

Conclusions

With regard to the two best-case series, this review supports the following conclusions:

• The IAT cases provide sufficient indications for the recommendation that IAT warrants further study.

• The naltrexone cases provide insufficient indications to determine the likely benefit for naltrexone at this time.

For IAT, this review suggests there is sufficient evidence to recommend that either a random controlled trial or a prospective case series could be considered. For naltrexone, a prospective cohort case series should be considered.

While the researchers' work demonstrates that a best-case series can be constructed for CAM therapy, it also demonstrates that to do so requires considerable resources, time, and effort. Assembling documentary evidence through retrospective case analysis is difficult, even with a trained research staff. The researchers encountered several difficulties trying to establish a “best-case” series: the quality of the records; confirmation of the diagnosis and the disease; documentation of treatment; self-selection of patients; and use of multiple treatment methods.

Future Research

This review was based on the assumption that a proactive approach by researchers to creating a best-case series might be more productive than relying on practitioners to create their own best-case series. The authors' review established that this work is extremely time consuming and expensive. This lead them to the conclusion that it is not feasible to expect health providers to create such a series—especially CAM providers, who may not be trained in research. An alternative approach might be to establish a prospective case series where the protocol for treatment and the documentation can be established prior to the treatment.

Purpose

Complementary and alternative medicine (CAM) is commonly tried by patients with cancer. However, evidence is lacking for the effectiveness of most CAM therapies for cancer. One of the challenges confronting the Cancer Advisory Panel on Complementary and Alternative Medicine (CAPCAM) is to identify promising CAM therapies that may have received insufficient consideration by the cancer research community. These include therapies that have not been subjected to a controlled trial, as well as those that have been subjected to a controlled trial but whose outcomes have either never been published or have been published only as a case study or a case series. As part of its mission, CAPCAM, in conjunction with the Office of Cancer Complementary and Alternative Medicine (OCCAM), provides a forum for practitioners to report on the outcomes of therapies and provides a resource for them to obtain technical assistance in developing best-case series studies. In best-case series studies, a provider chooses those cases that represent the best outcomes for a given form of treatment, and these cases are then reviewed by experts to determine if the evidence is sufficient to warrant further study. To assist in this effort, NCI has developed a set of criteria for creating a best-case series. For CAM therapies, CAPCAM has been charged with facilitating more rigorous investigation of therapies that show sufficient promise. Despite CAPCAM's efforts to publicize this forum, few case series have yet been presented to the panel. It was therefore decided that a proactive approach might be more productive in generating best-case series. Thus, the purpose of this study was to use the resources of the Southern California Evidenced-Based Practice Center (SCEPC) to create best-case series for therapies identified by the National Center for Complementary and Alternative Medicine (NCCAM).

Our purpose was to abstract patient records of a selected CAM provider and then to create a best-case series by evaluating each of the cases against a set of defined criteria. In addition, we report on the method, effort, and resources required to complete a best-case series and the practicality and feasibility of this method.

Specific Aims

The project had four specific aims, established by the National Center for Complementary and Alternative Medicine (NCCAM) and the Cancer Advisory Panel for Complementary and Alternative Medicine (CAPCAM):

1. To create best-case series for two CAM providers treating cancer patients.

2. To determine if there is sufficient evidence for recommending further study of these therapies.

3. To recommend the type of future study, if any.

4. To describe the technical challenges and difficulties in creating this kind of best-case series.

A Brief Review of the Use of CAM for Cancer Treatment

In the United States, the general public has increasingly sought out CAM therapies; about 40 percent of patients recently reported using some form of CAM (Eisenberg, Davis, Ettner, et al., 1998; Astin, 1998). Between 1990 and 1997, the prevalence of CAM use in the United States increased from 33.8 percent to 42.1 percent, and the number of visits to CAM practitioners increased from 427 million to 629 million visits per year (Eisenberg, Davis, Ettner, et al., 1998).

Among cancer patients, increasing interest in CAM has also been reported. Recent surveys of cancer patients in the United States estimated that 65 to 83 percent have tried some form of CAM therapy for their cancer (Richardson, Sanders, Palmer, et al., 2000; Boon, Stewart, Kennard, et al., 2000; Sparber, Bauer, Curt, et al., 2000). These figures exceed previously reported estimates (Burstein, Gelber, Guadagnoli, et al., 1999;Lerner and Kennedy, 1992; Cassileth, Lusk, Strouse, et al., 1984; Beckrow, Wyatt, Given, et al., 1999; Faw, Ballentine, Ballentine, et al., 1978; Adler and Foskett, 1999). A systematic review of 26 surveys across 13 countries concluded that the mean prevalence of CAM use by cancer patients in these countries was 31.4 percent (range, 7 percent to 64 percent) (Ernst and Cassileth, 1998).

The typical cancer patient using CAM in the United States is reported to be Caucasian, more affluent and better educated than average, 30 to 50 years of age, and suffering from advanced disease (Richardson, Sanders, Palmer, et al., 2000; Paltiel, Avitzour, Peretz, et al., 2001; Lerner and Kennedy, 1992; Cassileth, Lusk, Strouse, et al., 1984; Cassileth, 1986). National surveys of cancer patients found that dietary supplements (including vitamins, herbs, and substances that affect metabolism), electronic treatments, and mind/body approaches were the most popular (Richardson, Sanders, Palmer, et al., 2000; Lerner and Kennedy, 1992; Cassileth, Lusk, Strouse, et al., 1984). Studies report that most cancer patients (60 – 80 percent) who engage in CAM practices are simultaneously receiving conventional treatments (Cassileth, Lusk, Strouse, et al., 1984; Richardson, Sanders, Palmer, et al., 2000; McGinnis, 1991; Lerner and Kennedy, 1992; Bourgeault, 1996).

The growth in use of CAM in the United States is also supported by figures on expenditures for these treatments: out-of-pocket expenditures for 1997 were estimated at $;34.4 billion (Eisenberg, Davis, Ettner, et al., 1998), compared with a 1984 estimate of $4 billion spent annually on unproven cancer treatments (U.S. House Select Committee on Aging, 1984). A recent survey of women with breast cancer found that approximately $45 was spent monthly on CAM products and $55 was spent monthly on CAM practitioners (Boon, Stewart, Kennard, et al., 2000).

A variety of factors have prompted the increasing utilization of CAM among cancer patients. CAM use has been strongly associated with the belief among these patients that conventional therapy did not meet their needs (Paltiel, Avitzour, Peretz, et al., 2001). Patients have also reported concerns about the toxicity of conventional treatments, viewing CAM therapies as natural and nontoxic (Paltiel, Avitzour, Peretz, et al., 2001; Astin, 1998; Campion, 1993; Lerner and Kennedy, 1992). Despite this finding, another survey showed that approximately 60 percent of cancer patients who used CAM believed that conventional cancer treatments were more likely to cure their cancer than were CAM therapies (Boon, Stewart, Kennard, et al., 2000), and most patients used conventional medicine concurrently (Cassileth, Lusk, Strouse, et al., 1984; Richardson, Sanders, Palmer, et al., 2000; McGinnis, 1991; Lerner and Kennedy, 1992; Bourgeault, 1996). In a recent survey of cancer patients, the most common reason patients cited for using CAM was to boost their immune system (63 percent) (Boon, Stewart, Kennard, et al., 2000). Patients who use CAM also report feeling more hopeful (Richardson, Sanders, Palmer, et al., 2000). Although cancer patients often turn to CAM with the hope of improving their quality of life (Paltiel, Avitzour, Peretz, et al., 2001), some evidence suggests that users of CAM do not achieve that goal (Paltiel, Avitzour, Peretz, et al., 2001; Burstein, Gelber, Guadagnoli, 1999; Cassileth, Lusk, Guerry, et al., 1991). However, cancer patients who utilize CAM do report feeling more personal control over their situation (Richardson, Sanders, Palmer, et al., 2000), and patients assert that CAM use provides a feeling of control over their lives (Boon, Stewart, Kennard, et al., 2000).

Many patients who use CAM for any illness do not reveal that use to their physicians (Eisenberg, Davis, Ettner, et al., 1998; Adler and Foskett, 1999; Begbie, Kerestes, Bell, 1996). In a recent study of 1,221 breast cancer patients, fewer than half informed their physician of their CAM use (Boon, Stewart, Kennard, et al., 2000). Reasons for not disclosing CAM use include anticipating physician negative response, perceiving that CAM therapies are irrelevant to their conventional medical care, and believing that their physician is unable to contribute useful information about CAM (Adler and Foskett, 1999; Begbie, Kerestes, Bell, 1996). Some CAM users have expressed feeling abandoned by their physicians, and others admit having little faith in them (Cassileth, Lusk, Strouse, et al., 1984). Some patients reported a desire for CAM to be part of conventional cancer treatment (Coss, McGrath, Caggiano, 1998). Other reports indicate that cancer patients want more information about CAM from their medical doctors (Richardson, Ramirez, Nanney, et al., 1999).

Oncologists are becoming increasingly aware that patients use CAM, yet few oncologists discuss these therapies with their patients (Richardson, Ramirez, Nanney, et al., 1999; Neogi and Oza, 1998). This finding may stem from a number of factors. Research shows that the established medical community has been seeking evaluation of CAM therapies through traditional clinical trials (Angell and Kassirer, 1998, Levin, Glass, Kushi, et al., 1997), Without the evidence of efficacy such trials may provide, practitioners may be reluctant to broach the subject. Some physicians have expressed concerns about serious health risks associated with CAM and cite poor outcomes for patients who reject proven conventional cancer treatment in favor of CAM approaches (DiPaola, Zhang, Lambert, et al., 1998; Coppes, Anderson, Egeler, et al., 1998). However, since most cancer patients using CAM are receiving conventional treatments at the same time, it may be critical for oncologists to become more informed about use of CAM, because the effects of those conventional therapies may be influenced by concurrent CAM therapies.

Summary

The project involved a survey of two CAM cancer treatment sites identified by the NCCAM. Our project staff visited the two sites and asked CAM providers to identify their best cases. As the visitation team worked with the clinic staff physicians and reviewed the cases the latter had recommended, new cases suggested themselves to the clinic staff. These additional patient files were also screened by the visitation team based on the criteria for a best-case series established by the National Cancer Institute (NCI). The process of identifying the cases therefore was an interactive one. Promising cases were identified, and these patients were contacted to obtain permission for us to abstract their files. After consents were obtained, patients were interviewed by telephone; or if the patients were deceased, their next of kin were interviewed. All data collected from abstraction forms and the interview were summarized in a case report form. Cases identified as “best cases” based on NCI criteria, were further analyzed. All pertinent clinical data (radiologic scans, pathology slides) were identified, and clinical material was requested from the original institution. If the original clinical material was still available, it was sent to the Southern California Evidence-Based Practice Center (SCEPC).

A Best-Case Series

A “best-case series” differs from other forms of clinical evidence in that the cases are purposively selected because they are thought to be the best examples of improved patient outcomes as a result of treatment. In other words, cases are not selected randomly and are not representative of the “average” or “typical” case. Furthermore, there are no control cases that would facilitate a comparison of patient outcomes with and without the treatment in question —making it difficult, if not impossible, to establish a cause-and-effect relationship between treatment and outcome. A best-case series relies on assumptions about patient outcomes in the absence of treatment, and consequently requires very rigorous documentation of the patient's clinical status. This information is then used by clinical experts to make judgments about outcomes in similar patients treated with the best available conventional therapy. The difference in actual outcomes compared to this assessment of expected outcomes provides the basis for conclusions regarding the potential efficacy of the treatment in question. Best-case series are useful to help identify therapies that have sufficient promise of efficacy to justify the time and resources for more rigorous study, such as a clinical trial.

Study Design

1. 

   

   Figure 1. Research Sequence & Tasks

   

      Figure 1. Research Sequence & Tasks

   The project was conducted according to the following sequence (see Figure 1):

2. NCCAM identified two CAM providers who were treating cancer with a CAM therapy and secured their agreement to participate in the project.

3. The CAM providers were asked to identify their best cases, that is, those patients whom they judged benefited most from therapy.

4. The patients were contacted by the clinics to secure permission for their files to be reviewed, for the research team to contact them for an interview, and for permission to contact their other medical providers and request their patient files and records.

5. A research team from Southern California Evidence-Based Practice Center (SCEPC) visited both clinics to abstract patient files identified as potential best cases.

6. Following review of the patient abstraction records by the research staff, copies of the most promising patient files for inclusion in a best-case series were sent to SCEPC, where summaries of abstracted information were later checked against those files for accuracy.

7. The patients were interviewed to further confirm the medical information obtained from the charts, to identify any relevant medical information or procedures not previously identified, and to complete a Health-Related Quality of Life instrument.

8. Additional medical records were sought from the patients' other providers.

Development of the Instruments

Research Staff

Five trained abstractors (three physicians, one oncology nurse, and one medical sociologist) performed the chart abstraction in the clinics. The three physicians are board-certified internists, and two are directors of programs in integrative medicine and have expertise in CAM therapies. The third physician is director of a chronic-pain clinic and manages a multidisciplinary team that includes practitioners of alternative therapies. The nurse has practiced in oncology wards, hospices, and palliative care units in several countries for over 30 years. The medical sociologist is a health services researcher at RAND who has been involved in abstraction studies in chiropractic over the past 10 years. A fourth physician, also trained in integrative medicine and practicing CAM therapies, participated in writing the case reviews and the case reports. This physician and the medical sociologist, who was responsible for training the other staff, conducted all the patient interviews.

Data Sensitivity

Data collected for this project were private and sensitive. Data abstracted from medical records documenting the patients' cancer and their treatment as well as data collected from telephone interviews (name, phone number, age, gender, quality of life) contained information that could be damaging to the individuals if revealed. Furthermore, patients may not have wanted their providers of traditional care to know they were also receiving CAM treatment. If released, such information could possibly damage a patient's treatment, employment, and insurability. A data-safeguarding plan was instituted using guidelines established by RAND.

Clinic Visits

Overview of Case Review

For IAT, we reviewed, in depth, 30 cases (of the possible 60 cases) that had the potential to be included in a best-case series. Of those, nine cases are presented that we consider the most complete or appropriate in terms of the NCI criteria for a best-case series. They included the following types of cancer: Hodgkin's lymphoma, non - small cell carcinoma of the lung, nodular lymphoma (poorly differentiated), abdominal mesothelioma (two cases), ovarian adenocarcinoma, squamous cell carcinoma of vocal cord (two cases), and colon cancer.

For Naltrexone only three cases of the 21 we reviewed in depth approximated the NCI criteria. These included the following cancers: melanoma, pancreatic cancer, and endometrial adenocarcinoma with breast adenocarcinoma (single case).

However, the extent to which these cases meet the NCI criteria varied considerably. The most difficult criteria to meet are the histological/imaging confirmations, for two reasons; 1) inadequate information was provided by the file or the patient, or 2) the case was so old that the providers no longer had the specimens or files.

Table 1. Status report of requested materials (IAT) (more...)

Table 1. Status report of requested materials (IAT)

ID#	Authorization Received	Reports Requested	Status of Reports
1-1	Yes	6 requested	1 pending
			5 not available
1-3	Yes	1 requested	1 not available
1-4	Yes	6 requested	6 pending
1-6	Yes	7 requested	7 not available
1-7	Yes	9 requested	7 received
			1 pending
			1 not available
1-9	Yes	6 requested	2 received
			4 not available
1-11	Yes	1 requested	1 not available
1-19	Yes	5 requested	2 pending
			3 not available
1-22	Yes	6 requested	6 pending

Table 2. Status report of requested materials (Naltrexone) (more...)

Table 2. Status report of requested materials (Naltrexone)

ID#	Authorization Received	Reports Requested	Status of Reports
2-10	Yes	2 requested	2 pending
2-21	Yes	4 requested	4 pending
2-22	Yes	9 requested	9 pending

Cancer Best-Case Series

Patient #1-1 Nodular Sclerosing Lymphoma Stage 1B

Case 1-1

The patient in case 1-1 is a 46-year-old male diagnosed on 12/2/83 with nodular sclerosing lymphoma stage 1B after presenting with superior vena caval obstruction. Palliative radiation therapy was completed on 12/7/83 with a total of 800 RADS delivered to his vena cava. Chemotherapy (MOPP) was started on 12/00/83 and stopped early on 6/00/84. Four cycles of full-dose chemotherapy and two additional courses of a 25% reduced dose were given. On 7/19/94, it was recommended that the patient receive full mantle radiation, which he declined. At the termination of conventional therapy, the patient had no palpable peripheral lymphadenopathy but still had a superior mediastinal mass (CXR 7/10/84). IAT was started on 8/2/84, and 22 courses were completed as of 12/8/00 (the data of chart abstraction). The patient had sporadically taken a variety of dietary supplements in the past. Serial chest x-rays performed during IAT therapy showed a decrease in tumor mass. The most recent MRI for which we have a report (11/4/86) showed inactive disease. The most recent MRI of the chest (1995) revealed no tumor according to the patient. At the last patient contact (interview, 9/26/01), the patient reported that his overall physical condition was excellent.

Pathology

12/2/83	Biopsy: anterior mediastinal Hodgkin's lymphoma (nodular sclerosing type)
12/7/83	Biopsy: bone marrow: normal

Imaging

4/17/84	X-ray chest: further improvement of mediastinal mass
7/10/84	X-ray chest: mass in chest, no change
11/4/86	MRI chest: complete obstruction of superior vena cava. Unchanged anteromediastinal mass suggests inactive disease at this time
1995	MRI chest: no evidence of disease per patient

Conventional therapy

12/7/83	Radiation: palliative to superior vena cava: 800 RADS: decrease in size of mass
12/83–6/84	Chemotherapy: MOPP: 4 cycles: followed by 2 cycles reduced by 25%: Did not complete chemotherapy due to patient preference and low blood counts.
7/19/84	Radiation (mantle) recommended; patient declined

Complementary therapy

8/2/84–12/8/00	IAT 22 courses
11/1/84	Benzaine E, calcium orotate, molybdenum, S.O.D., beta-carotene, glutathione, kyolic, Vitamin C, Vitamin E, lithumorate, Wobenzym, inzellonal, transmutase forte, thymus pills & injections, asterile injections, beriglobin, Vitamin D oil, selenium, carnitine (treatment recorded as provided by patient)
Date unknown	Live cell therapy in Germany; did not proceed with entire treatment

Patient # 1-1
EVENT	PERIOD 1				PERIOD 2				PERIOD 3				PERIOD 4				PERIOD 5				PERIOD 6
	1st qtr 1983 – 4th qtr 1983				1st qtr 1984 – 4th qtr 1984				1st qtr 1985 – 4th qtr 1985				1st qtr 1986 – 4th qtr 1986				1st qtr 1995 – 4th qtr 1995				1st qtr 2000 – 4th qtr 2000
Biopsy/diagnosis				12/83
Surgery
Radiation				12/83
Chemotherapy				12/83		6/84
IAT							8/84																	12/00
CAM other								11/84
Imaging CXR					3/84	4/84	7/84
Imaging MRI																11/86	1995

Date	Description of Events	Requested	Status of requests
	Family history of lymphoma in brother
12/2/83	Biopsy: anterior mediastinal: Hodgkin's disease (nodular sclerosing)	Slides	Not avail.
12/7/83	Biopsy: bone marrow; normal	Slides	Not avail.
12/7/83	Radiation: palliative to superior vena cava: 800 RADS: decrease in size of mass
12/83–6-84	Chemotherapy: MOPP: 4 cycles: followed by 2 cycles reduced by 25%: Did not complete chemotherapy due to patient preference.
4/17/84	X-ray chest: further improvement of mediastinal mass	Films	Not avail.
7/10/84	X-ray chest: mass in chest, no change	Films	Not avail.
8/2/84–12/8/00	IAT 22 courses
11/1/84	Benzaine E, calcium ortate, molybenum, S.O.D., beta-carotene, glutathione, kyolic, Vitamin C, Vitamin E, lithumorate, wobenzym, inzellonal, tranmusase forte, thymus pills & injections, astenile injections, beriglobin, Vitamin D oil, selenium, carnitine
11/4/86	MRI chest: complete obstruction of superior vena cava. Inactive disease at this time	Films	Not avail.
1995	MRI chest: no evidence of disease per patient	Films	Pending

Patient #1-3 Squamous Cell Carcinoma of the Right Vocal Cord and Anterior Commissure

Case 1-3

The patient in case 1-3 is a 68-year-old male who was diagnosed with squamous cell carcinoma of the right vocal cord and anterior commissure on 9/3/81. An excisional biopsy was performed at that time, but the resection was not complete. The patient was referred for radiation therapy, which he refused due to patient preference. Thus, the patient received no definitive conventional therapy. He completed 15 courses of IAT from 9/22/81 to 5/19/89. Serial examinations by his otolaryngologist revealed the persistent presence of disease without progression through 2/23/82. An otolaryngologist performed an indirect laryngoscopy on 7/20/94, which did not reveal any abnormal findings. At the last contact (interview, 9/24/01), the patient reported that his overall physical condition was very good to excellent.

Pathology

9/3/81

Biopsy: squamous cell carcinoma, well differentiated, infiltrating: right vocal cord and anterior commissure: stage T:1 1/2 N:0 M:0

Imaging

9/22/81	X-ray chest: normal
7/20/94	ENT evaluation visual inspection via indirect laryngoscopy: normal exam

Conventional therapy

9/3/81	Surgery: biopsy with debulking; 80–90% bulky tumor mass removed; residual cancer remained
9/16/81	Referred for radiation: patient refused

Complementary therapy

9/22/81–5/19/89

IAT 15 courses

Patient # 1-3
EVENT	PERIOD 1				PERIOD 2				PERIOD 3				PERIOD 4				PERIOD 5				PERIOD 6
	1st qtr 1981 – 4th qtr 1981				1st qtr 1984 – 4th qtr 1984				1st qtr 1985 – 4th qtr 1985				1st qtr 1986 – 4th qtr 1986				1st qtr 1989 – 4th qtr 1989				1st qtr 1994 – 4th qtr 1994
Diagnosis/biopsy			9/81
Diagnostic procedure																							7/94
Surgery			9/81
Radiation
Chemotherapy
IAT			9/81															5/89
CAM other
Imaging CXR			9/81

Date	Description of Events	Requested	Status of requests
	Family history of gastric cancer in mother
9/3/81	Biopsy: squamous cell carcinoma, well-differentiated, infiltrating: right vocal cord and anterior commisure: stage T:1 1/2 N:0 M:0	Slides	Not avail.
9/3/81	Surgery: biopsy with debulking- residual cancer remained
9/3/81	Referred for radiation: patient refused
9/22/81	X-ray chest: normal
9/22/81–5/19/89	IAT: 15 courses
7/20/94	ENT evaluation visual inspection via indirect laryngoscopy

Patient #1-4 Metastatic Non - Small Cell Carcinoma of the Lung

Case 1-4

The patient in case 1-4 is a 67-year-old woman with a family history of cancer, diagnosed with metastatic non - small cell carcinoma of the lung in July 1992. She initially presented with swelling in the neck, an enlarged supraclavicular lymph node, and a chest mass demonstrated by CT in the area of the aortic notch. A mini-thoracotomy was performed to obtain tissue for diagnosis. Initially, the mass was identified as an anaplastic mediastinal tumor, which subsequent review at the Canadian Reference Lab for Pathology determined to be non - small cell poorly differentiated lung cancer. Subsequently, she was referred for palliative chemotherapy and radiation, which she completed. No response was demonstrated to these treatments, and no further conventional therapy was advised. She initiated IAT in February 1993 and continues on maintenance therapy today. Serial CT scans beginning in September 1994 revealed resolution of the tumor. At the last contact (interview, 12/4/01), the patient reported that her overall physical condition was good.

Pathology

7/31/92	Surgical biopsy: mediastinum (multiple bite biopsy via mediastinotomy): discrepancy of pathological diagnosis: first diagnosis lymphoma, second diagnosis metastatic giant cell carcinoma, third diagnosis lung carcinoma poorly differentiated (9/4/92)
7/31/92	Biopsy: left supraclavicular lymph node final pathology revealed lung carcinoma poorly differentiated
8/12/92	Biopsy: bone marrow: negative for malignancy

Imaging

July, 92	CT scan thorax: tumor 5cm mass in the area of the aortic notch
7/31/92	X-ray chest: no change compared with prior
8/4/92	Bone scan whole body: no metastatic bone disease
9/9/93	CT scan thoracic: tumor decreased in size, residual tumor or post treatment fibrosis
11/30/93	X-ray chest/ left shoulder: right lung clear; no tumor; increase left hemi-diaphragm
4/13/94	X-ray chest: no significant changes compared with previous
9/26/94	X-ray chest: lungs clear
9/26/94	CT scan thoracic: no evidence of tumor; Remission based on CT scan of thorax revealing no evidence of tumor
6/24/93	Ultrasound abdomen: normal
11/11/96	CT scan thoracic: no evidence of tumor; post radiation changes in left thorax
11/25/97	CT scan thoracic: no evidence of tumor
12/7/98	CT scan thoracic: no evidence of tumor
12/15/00	CT scan thoracic: no evidence of tumor; no change compared with 12/7/98

Conventional therapy

7/31/92	Left anterior mediastinotomy; mediastinal mass biopsy
8/00/92	Chemotherapy: cytoxan, adriamycin, vincristine, prednisone; stopped early due to change in tissue diagnosis
9/00/92	Chemotherapy: VP16 190mg, cisplatinum 48 mg : 3 days every 3 weeks: completed recommended course: no tumor response
10/21/92	Radiation: palliative: mediastinum/ left perihilar/ supraclavicular: 4,000cGy; no tumor response
11/92–12/92	Chemotherapy: VP16 190mg, cisplatinum 48 mg: 3 days every 3 weeks: completed recommended course: no tumor response

Complementary therapy

2/8/93-present

IAT; still on maintenance therapy

Patient # 1-4
EVENT	PERIOD 1				PERIOD 2				PERIOD 3				PERIOD 4				PERIOD 5				PERIOD 6				PERIOD 7				PERIOD 8				PERIOD 9				PERIOD 10
	1st qtr 1992 – 4th qtr 1992				1st qtr 1993 – 4th qtr 1993				1st qtr 1994 – 4th qtr 1994				1st qtr 1995 – 4th qtr 1995				1st qtr 1996 – 4th qtr 1996				1st qtr 1997 – 4th qtr 1997				1st qtr 1998– 4th qtr 1998				1st qtr 1999 – 4th qtr 1999				1st qtr 2000 – 4th qtr 2000				1st qtr 2001 – 4th qtr 2001
Diagnosis/biopsy			7/92, 8/92
Surgery			7/92
Radiation				10/92
Chemotherapy			7/92–9/92	12/92
IAT					2/93
CAM other
Imaging CXR			7/92					11/93		4/94	9/94
Imaging CT			7/92				9/93				9/94									11/96				11/97				12/98								12/00
Imaging bone scan			8/92

Date	Description of Events	Requested
no date	Family history: sister lung cancer, maternal aunt breast cancer, mother urinary cancer
7/31/92	Surgical biopsy: mediastinum (multiple bite biopsy via mediastinotomy): discrepancy of pathological diagnosis: first diagnosis lymphoma, second diagnosis metastatic giant cell carcinoma, third diagnosis lung carcinoma poorly differentiated (9/4/92)	Slides
7/31/92	Biopsy: left supraclavicular lymph node final pathology revealed lung carcinoma poorly differentiated	Slides
7/31/92	X-ray chest: no mass
8/4/92	Bone scan whole body: no metastatic bone disease
8/12/92	Biopsy: bone marrow: negative for malignancy
8/00/92	Chemotherapy: cytoxan, adriamycin, vincristine, prednisone; stopped early due to change in tissue diagnosis
9/00/92	Chemotherapy: VP16 190mg, cisplatinum 48 mg : 3 days every 3 weeks: completed recommended course: no tumor response
10/21/92	Radiation: palliative: mediastinum/ left perihilar/ supraclavicular: 4,000cGy; no tumor response
1/6/93	Chemotherapy: VP16 190mg, cisplatinum 48 mg : 3 days every 3 weeks: completed recommended course: no tumor response
2/8/93-present	IAT; still on maintenance therapy
6/24/93	Ultrasound abdomen: normal
9/9/93	CT scan thoracic: tumor decreased in size, residual tumor or post treatment fibrosis	Films
11/30/93	X-ray chest/ left shoulder: right lung clear; no tumor; increase left hemi-diaphragm
4/13/94	X-ray chest: no significant changes compared with previous

Date	Description of Events	Requested	Status of requests
9/26/94	X-ray chest: lungs clear	Films	Pend.
9/26/94	CT scan thoracic: no evidence of tumor
11/11/96	CT scan thoracic: no evidence of tumor; post radiation changes in left thorax
11/25/97	CT scan thoracic: no evidence of tumor
7/12/98	CT scan thoracic: no evidence of tumor	Films	Pend.
12/15/00	CT scan thoracic: no evidence of tumor; no change compared with 12/7/98	Films	Pend.

Patient #1-6 Poorly Differentiated Nodular Lymphoma

Case 1-6

The patient in case 1-6 is a 49-year-old male who was diagnosed in 1983 with poorly differentiated nodular lymphoma after presenting with an enlarged node on his chin, fever, night sweats, and generalized pruritus. Although the patient was not found to have significant demonstrable adenopathy outside of the neck at diagnosis, he was felt to represent stage II disease. Local radiation was not recommended, and chemotherapy was deferred awaiting progression of disease. By 2/1/84, he had palpable adenopathy in both axillae and demonstrated anergy in skin testing. The patient elected to try unconventional therapy. He started IAT on 2/14/84 and had completed twelve courses by 7/19/90. He is currently in remission. At last contact (interview, 11/07/01), the patient reported that is overall physical condition was excellent.

Pathology

12/5/83	Biopsy: pathology: lymph node: poorly differentiated lymphocytic nodular lymphoma
12/21/83	Biopsy: bone marrow: negative for malignancy

Imaging

12/4/83	Chest x-ray: within normal limits
12/21/83	Chest x-ray: within normal limits
12/21/83	Ultrasound abdomen: within normal limits
2/14/84	Ultrasound abdomen: within normal limits
2/14/84	Chest x-ray: within normal limits
3/23/88	Ultrasound abdomen: within normal limits

Complementary therapy

2/14/84–7/19/90

IAT: 12 courses

Conventional therapy

None

Patient # 1-6
EVENT	PERIOD 1				PERIOD 2				PERIOD 3				PERIOD 4				PERIOD 5				PERIOD 6
	1st qtr 1983 – 4th qtr 1983				1st qtr 1984 – 4th qtr 1984				1st qtr 1985 – 4th qtr 1985				1st qtr 1986 – 4th qtr 1986				1st qtr 1988 – 4th qtr 1988				1st qtr 1990 – 4th qtr 1990
Diagnosis/biopsy				12/83
Surgery
Radiation
Chemotherapy
IAT					2/84																		7/90
CAM other
Imaging CXR				12/83, 12/83	2/84
Imaging ultrasound				12/83	2/84												3/88

Date	Description of Events	Requested	Status of requests
no date	Family history of cancer: mother died age 32 melanoma; father died age 57 of lung cancer
12/5/83	Biopsy: diagnostic excisional biopsy: poorly differentiated lymphocytic nodular lymphoma	Slides	Not avail.
12/21/83	Bone marrow: negative for malignancy
12/21/83	Ultrasound abdomen: within normal limits	Films	Not avail.
12/4/83	Chest x-ray: within normal limits	Films	Not avail.
12/21/83	Chest x-ray: within normal limits	Films	Not avail.
2/14/84	Chest x-ray: within normal limits	Films	Not avail.
2/14/84–7/19/90	IAT: 12 courses
3/23/88	Ultrasound abdomen: within normal limits	Films	Not avail.
6/20/98	Physical exam: peripheral lymphadenopathy resolved by 1988: negative radiological studies

Patient #1-7 Peritoneal Mesothelioma

Case 1-7

The patient in case 1-7 is a 50-year-old Caucasian female with a history of peritoneal mesothelioma. She was initially misdiagnosed with ovarian cancer on 7/1/99 after peritoneal biopsies were obtained from an exploratory laparoscopy with excision of left pelvic mass, left colectomy, colostomy, and omentectomy. Given the diagnosis of ovarian cancer, chemotherapy was initiated with taxol and carboplatin on 7/28/99. She had an anaphylactic reaction to taxol, and chemotherapy was stopped. On 8/5/99, the biopsies were again reviewed at the Armed Forces Institute of Pathology, and a diagnosis of peritoneal mesothelioma was made. No other conventional therapy was pursued due to patient preference. IAT was started on 12/1/99 and continued, with her most recent treatment on 6/6/01. Serial pelvic CT scans reveal a gradual diminution of pelvic densities, with the most recent pelvic CT scan on 5/24/01 revealing no evidence of progressive tumor or other abnormality. On 10/24/01, an attempt was made to reverse the patient's colostomy. Reversal was not possible due to adhesions, and the patient's small bowel was nicked, leading to a complicated post-operative course. However, according to the patient, the surgeon reported a decrease in the tumor bulk based on visual inspection. At last contact (interview, 9/26/01), the patient reported that her overall physical health is good.

Pathology

7/1/99	Pathology: ovarian carcinoma vs. mesothelioma melanoma
8/5/99	Pathology: final diagnosis: malignant mesothelioma (same tissue specimen)

Imaging

2/29/00	CT scan of abdomen and pelvis: no associated definitive soft tissue mass to suggest progression or recurrence of disease, no evidence of lymphadenopathy
5/19/00	CT scan of abdomen and pelvis: abdomen-no recurrent mass, no definite associated soft tissue mass effect, pelvis-increase in fluid collection L>R c/w 2/29/00.
8/10/00	X-ray chest: normal
8/30/99	CT scan of pelvis: decrease in soft tissue density and fluid c/w 6/28/99
9/12/00	CT scan of abdomen and pelvis: small nodular densities adjacent to the spleen, fluid collection right side of pelvis not decreased, left side extension no longer identified
11/14/00	Bone scan whole body: prominent activity in right renal pelvis similar to 2/98
12/15/00	US RUQ: no abnormality, no change from prior
1/16/01	CT scan of abdomen and pelvis with contrast: no bowel abnormalities, fluid collection on right side has increased to 4.5x3cm, now fluid to lower pelvis left side, findings nonspecific but recurrence possible
1/23/01	CT scan of pelvis: increased size of 2 rounded densities in pelvis, right lateral pelvic wall 4.5x3x0.15cm
1/23/01	CT scan of abdomen: mild prominence of left adrenal unchanged
3/9/01	CT scan of abdomen and pelvis with contrast: abdomen unremarkable, pelvis with loculated fluid collection in inferior pelvis in midline and on right, slight reduction in size
5/24/01	CT scan of abdomen: no pathologically enlarged lymph nodes or free fluid
5/24/01	CT scan of pelvis: no evidence of progressive tumor or abnormality; significant interval reduction of irregularly loculated fluid collections compared with 3/9/01 consistent with response of mesothelioma
8/15/01	CT scan of abdomen: no upper abdominal mass compared with 5/24/01
8/15/01	CT scan of pelvis; further reduction in small amounts of fluid. No evidence of progressive neoplasm compared with 5/24/01

Tumor markers

7/23/99	CAa 125 = 22 (<35)
5/16/00	CA 125 = 13 (<35)

a

Cancer Antigen.

Conventional therapy

7/1/99	Exploratory laparoscopy with excision of left pelvic mass, left colectomy, colostomy, omentectomy, and multiple peritoneal biopsies
7/28/99	Taxol, carboplatin (initially thought to be ovarian cancer) stopped due to anaphalaxis
10/24/01	Surgery: attempted reversal of colostomy: decrease of tumor bulk based on visual inspection

Complementary therapy

12/1/99–6/6/01	IAT 6 courses over this time interval
12/1/99-present (intermittent)	MGn3, noni juice, colostrum, vitamin E, green tea, vitamin C, beta carotene, cat's claw, homeopathic miasms
1/30/01-present (intermittent)	Homeopathic -Haelan (fermented soy product), cat's claw, lyperinol
2/2/01-present (intermittent)	Illumination: multiherbal combo, Universal Complex (echinacea mix), Circu-Plus (gingko, ginseng), Mg/K aspartate, alpha-oxzyme, LSK Plus (granular liver, spleen, kidney)

Patient # 1-7
EVENT	PERIOD 1				PERIOD 2				PERIOD 3
	1st qtr 1999 – 4th qtr 1999				1st qtr 2000 – 4th qtr 2000				1st qtr 2001 – 4th qtr 2001
Diagnosis/biopsy			7/99
Surgery			7/99									10/01
Radiation
Chemotherapy			7/99
IAT				12/99						6/01
CAM other				12/99					1/01, 2/01
Imaging CT scan					2/00	5/00	9/00		1/01, 3/01	5/01	8/01
Imaging CXR							8/00
Imaging ultrasound								12/00
Tumor marker						5/00

Date	Description of Events	Requested	Status of request
6/28/99	CT scan of pelvis: 3.5cm cystic left adnexal mass	Films	Rcvd.
7/1/99	Exploratory laparoscopy with excision of left pelvic mass, left colectomy, colostomy, omentectomy, multiple peritoneal biopsies.
7/1/99	Pathology: Ovarian carcinoma vs. malignant melanoma
7/23/99	CA 125 = 22 (<35)
7/28/99	Taxol, carboplatin (initially diagnosed with ovarian cancer)
7/28/99	Adverse event: anaphylaxis from taxol
8/5/99	Pathology: final diagnosis: malignant mesothelioma (same tissue sample)	Slides	Pend.
8/30/99	CT scan of pelvis: decrease in soft tissue density and fluid c/w 6/28/99	Films	Rcvd.
9/24/99	PET scan of whole body: no specific findings to suggest residual tumor in torso, increased activity small area in neck
2/29/00	CT scan of abdomen and pelvis: no associated definitive soft tissue mass to suggest progression or recurrence of disease, no evidence of lymphadenopathy
5/16/00	CA 125 = 13 (<35)
5/19/00	CT scan of abdomen and pelvis: abdomen-no recurrent mass, no definite associated soft tissue mass effect, pelvis-increase in fluid collection L>R c/w 2/29/00.
8/10/00	X-ray chest: normal
9/12/00	CT scan of abdomen and pelvis: small nodular densities adj. to spleen, fluid collection right side pelvis not decr., left side extension no longer identified	Films	Not avail.
11/14/00	Bone scan of whole body: no change c/w 2/98
11/14/00	X-ray chest: within normal limits
12/15/00	US RUQ: no abnormality, no change from 6/29/99
1/16/01	CT scan of abdomen and pelvis with contrast: no bowel abnormalities, fluid collection on right side has increased to 4.5x3cm, now fluid to lower pelvis left side, findings nonspecific but recurrence possible
1/23/01	CT scan of pelvis: increased size of 2 rounded densities in pelvis, right lateral pelvic wall 4.5x3x0.15cm
3/9/01	CT scan of abdomen and pelvis with contrast: abdomen unremarkable, pelvis with loculated fluid collection in inferior pelvis in midline and on right, slight reduction in size
5/24/01	CT scan of abdomen: no pathologically enlarged lymph nodes or free fluid	Films	Rcvd.
5/24/01	CT scan of pelvis: no evidence of progressive tumor or abnormality
12/1/1999 6/6/01	IAT 5 courses
12/1/1999-present (intermittent)	Mgn3, noni juice, colostrum, vitamin E, green tea, vitamin C, beta carotene, cat's claw, homeopathic miasms
1/30/2001-present (intermittent)	Homeopathic - not specified, Haelan (fermented soy product), cat's claw, lyperinol
2/2/2001- present (intermittent)	Illumination: multiherbal combo, Universal Complex (echinacea mix), Circu-Plus (ginko, ginseng), Mg/K aspartate, alpha-oxzyme, LSK Plus (granular liver, spleen, kidney)
8/15/01	CT scan abdomen: no upper abdominal mass compared to 5/24/01.	Films	Rcvd.
8/15/01	CT scan of pelvis; further reduction in small amounts of fluid. No evidence of progressive neoplasm compared with 5/24/01	Films	Rcvd.
10/12/01	CT scan of abdomen and CT scan of pelvis with contrast: high grade partial small bower obstruction. No discrete mass is visualized, however, there is free intraperitoneal air with an air fluid level.	Films	Rcvd.
10/17/01	CT scan of abdomen and CT scan of pelvis with contrast: small bowel dilation slightly less prominent than previously seen, otherwise basically unchanged compared to previous examination.	Films	Rcvd.
10/24/01	Surgery: attempted reversal of colostomy: decrease of tumor bulk based on visual inspection

Patient #1-9 Ovarian Cyst Adenocarcinoma

Case 1-9

The patient in case 1-9 is a 54-year-old woman with ovarian cyst adenocarcinoma diagnosed on 5/3/80. She had a total abdominal hysterectomy with bilateral salpingo-oophorectomy with debulking at that time. Subsequently, she was referred for chemotherapy but refused due to patient preference. Her only therapy has been 34 courses of IAT from 6/3/80 to 6/12/99. In June 1987, a CT scan revealed lesions in her liver suspicious for metastatic disease. A liver biopsy was recommended, but since a needle biopsy was not possible due to adhesions, none was performed. Subsequent followup did not reveal progression of disease. A pelvic mass was noted on 8/6/00 and found to be increasing over the next year to a maximal dimension of 2.8cm × 2.8cm. An exploratory laparotomy with resection of left pelvis mass and biopsy of right pelvis was performed on 6/29/81. Pathology from the surgery was negative. Tumor markers have also been negative. Routine gynecologic care has not revealed any abnormalities. At last contact (interview, 10/09/01), the patient reported that her overall physical health was good.

Pathology

5/3/80	Biopsy: right ovary: papillary cyst adenocarcinoma, left ovary: same diagnosis
6/29/81	Biopsy: excision of pelvic mass—no tumor
6/14/90	Pap smear cytology: negative for malignancy
6/12/91	Pap smear cytology: negative for malignancy

Imaging

5/1/80	Ultrasound: pelvis mass 9cm × 7cm
5/21/80	Liver scan: normal
5/23/80	Bone scan whole body: normal
8/6/80	Ultrasound: pelvis cystic left adnexal mass 2cm × 2.5cm, no fluid in pelvis
9/24/80	Ultrasound: pelvis cystic left adnexal mass present since 8/6/80 unchanged
12/10/80	Ultrasound: pelvis cystic left adnexal mass present since 8/6/80 slightly smaller
1/28/81	Bone scan whole body: new area of increased uptake left iliac crest since 5/23/80
4/20/81	Ultrasound: pelvis cystic left adnexal mass 2.3cm unchanged c/w 12/10/80
4/22/81	Bone scan whole body: diffuse uptake in skull; increased uptake lumbar spine consistent with osteoarthritis: no evidence of metastases
6/8/81	Ultrasound: pelvis cystic left adnexal mass 2.8cm × 2.8cm, increased since 4/20/81
9/8/81	Ultrasound: pelvis no adnexal mass present, no fluid present
6/1/83	Ultrasound: pelvis no adnexal mass present, no fluid present
1/15/86	Ultrasound: pelvis no adnexal mass present, no fluid present
6/10/87	CT scan abdomen: suspicious for liver metastases; focal areas of low attenuation throughout liver
3/4/91	X-ray chest no change c/w 8/9/89
5/31/91	Mammogram breast: normal
5/27/92	Mammogram breast: normal
8/6/1993	MRI thoracic spine: osteoporosis

Tumor markers

5/30/90	CAa-125: <7.5 (normal 0–35)
5/29/91	CA-125: 6.3 (normal 0–35)
5/6/94	CA-125: <8.0 (normal 0–35)
6/10/97	CA-125 = 5.0 (0–35); CEAb = 0.3 (0–3)
6/11/01	CA-125 = 6.0 (0–35)

a

CA: Cancer Antigen.

b

CEA: Carcinoembrionic Antigen.

Conventional therapy

5/1/80	Surgery: TAH/BSO with appendectomy
5/3/80	Chemotherapy recommended: never started
6/29/81	Surgery: exploratory laparotomy with resection of left pelvic mass and biopsy

Complementary therapy

6/3/80–6/12/99

IAT: 34 courses over this time period; no home maintenance after 16 courses

Patient # 1-9
EVENT	PERIOD 1				PERIOD 2				PERIOD 3				PERIOD 4				PERIOD 5				PERIOD 6				PERIOD 7				PERIOD 8				PERIOD 9				PERIOD 10				PERIOD 11				PERIOD 12
	1st qtr 1980 – 4th qtr 1980				1st qtr 1981 – 4th qtr 1981				1st qtr 1983 – 4th qtr 1983				1st qtr 1986 – 4th qtr 1986				1st qtr 1987 – 4th qtr 1987				1st qtr 1989 – 4th qtr 1989				1st qtr 1990– 4th qtr 1980				1st qtr 1991 – 4th qtr 1991				1st qtr 1994 – 4th qtr 1994				1st qtr 1997 – 4th qtr 1997				1st qtr 1999 – 4th qtr 1999				1st qtr 2001 – 4th qtr 2001
Diagnosis/biopsy		5/80				6/81
Surgery		5/80				6/81
Radiation
Chemotherapy
IAT		6/80																																								6/99
CAM other
Imaging CXR																													3/91
Imaging ultrasound		5/80	8/80, 9/80	12/80		4/81, 6/81	9/81			6/83			1/86
Imaging CT																		6/87
Tumor markers																										5/90				5/91				5/94				6/97								6/01
Bone scan		5/80			1/81	4/81
Pap smear																										6/90				6/91

Date	Description of Events	Requested	Status of requests
	Mother-carcinoma of the uterus, grandmother-lung cancer, grandfather-cancer of tongue, brother-leukemia
5/1/80	Ultrasound: mass in pelvis 9cm × 7cm	Films	Not avail.
5/3/80	Surgery: TAH/BSO with appendectomy
5/3/80	Biopsy:right ovary: papillary cystadenocarcinoma ; left ovary same diagnosis	Slides	Not avail.
5/3/80	Chemotherapy recommended: never started
5/21/80	Liver scan: normal
5/23/80	Bone scan whole body: normal
6/3/80–6/12/1999	IAT: 34 courses over this time period; no home maintenance after 16 courses
8/6/80	Ultrasound: pelvis cystic left adnexal mass 2cm × 2.5cm, no fluid in pelvis	Films	Not avail.
9/24/80	Ultrasound: pelvis cystic left adnexal mass present since 8/6/80 unchanged
12/10/80	Ultrasound: pelvis cystic left adnexal mass present since 8/6/80 slightly smaller
1/28/81	Bone scan whole body: new area of increased uptake left iliac crest since 5/23/80
4/20/81	Ultrasound: pelvis cystic left adnexal mass 2.3cm unchanged c/w 12/10/80	Films	Not avail.
4/22/81	Bone scan whole body: diffuse uptake in skull; increased uptake lumbar spine consistent with osteoarthritis: no evidence mets
6/8/81	Ultrasound: pelvis cystic left adnexal mass 2.8cm × 2.8cm, increased since 4/20/81
6/29/81	Surgery: exploratory laparotomy with resection of left pelvic mass and biopsy	Slides	Rcvd.
6/29/81	Biopsy: excision of pelvic mass- no tumor
9/8/81	Ultrasound: pelvis no adnexal mass present, no fluid present
6/1/83	Ultrasound: pelvis no adnexal mass present, no fluid present
1/15/86	Ultrasound: pelvis no adnexal mass present, no fluid present	Films	Not avail.
6/10/87	CT scan abdomen: suspicious for liver mets; focal areas of low attenuation throughout liver	Films	Not avail.
Jun-87	Biopsy of liver lesions recommended but not performed; needle biopsy not possible due to adhesions
5/30/90	CA-125: <7.5 (normal 0–35)
6/14/90	Pap smear cytology: negative for malignancy
3/4/91	X-ray chest no change c/w 8/9/89
5/29/91	CA-125: 6.3 (normal 0–35)
5/31/91	Mammogram breast: normal
6/12/91	Pap smear cytology: negative for malignancy
5/27/92	Mammogram breast: normal
8/6/93	MRI thoracic spine: osteoperosis
5/4/94	CA-125: <8.0 (normal 0–35)
6/10/97	CA-125 = 5.0 (0–35); CEA = 0.3 (0–3)
6/11/01	CA-125 = 6.0 (0–35)
present	Routine physical exams/ serial CA-125 normal per patient during interview

Patient #1-11 Peritoneal Mesothelioma

Case 1-11

The patient in case 1-11 is a 59-year-old male with a family history of breast cancer, diagnosed in May, 1980 with peritoneal mesothelioma after presenting with a history of right lower quadrant abdominal pain and dyspepsia. His work-up included a cholangiogram, upper GI series with a small bowel follow-through, and an intravenous pyelogram of the GU tract. After these tests returned normal, a small bowel obstruction was the leading diagnosis until an exploratory laparotomy revealed peritoneal mesothelioma. According to the operative report (5/8/80), there was widespread disease throughout the pelvic and abdominal cavities. A partial omentectomy was performed, and as much bulk disease was removed as possible. A second opinion was obtained at MD Anderson (6/16/80 – 6/23/80), and it was recommended that additional tissue be obtained to confirm the diagnosis of mesothelioma via electron microscopy, which was done on 6/25/80. Due to the lack of a definitive curative therapy, no specific recommendations for chemotherapy, radiation, or future surgery were made. The patient started IAT therapy on 7/22/80 and completed the course in 5/84. At last contact (interview, 9/19/01), the patient reported that his overall physical condition is very good.

Pathology

5/8/80	Pathology of cysts on peritoneum: mesothelioma of peritoneum, multiple sites
6/25/80	Pathology: electron microscopy: multiple cystic mesothelioma of peritoneum

Imaging

4/11/80	IVP of GU tract: within normal limits
4/12/80	IV cholangiogram: within normal limits
4/12/80	UGI with SBF: within normal limits
4/14/80	Barium enema: within normal limits
4/16/80	CT scan of abdomen: within normal limits
4/20/80	X-ray chest: collapse of portion LLL, air containing structure posterior to sternum; nodular density adj. to left hilum
4/22/80	Tomogram of left lung: possible mass adjacent to hilum is “distorted branch of pulmonary artery”
5/10/80	X-ray chest: left ventricular enlargement
5/16/80	Bone scan of total body: within normal limits
5/17/80	Liver and spleen scan: within normal limits

Conventional therapy

5/8/80

Surgery: exploratory laparoscopy, excision of multiple cysts, subtotal omentectomy for palliative: most of peritoneal cavity lined with cysts. Debulking done. Tumor is cystic, grape-like, no ascites.

Complementary therapy

7/22/80–7/20/84

IAT 16 courses

Patient # 1-11
EVENT	PERIOD 1				PERIOD 2				PERIOD 3				PERIOD 4				PERIOD 5				PERIOD 6
	1st qtr 1980 – 4th qtr 1980				1st qtr 1981 – 4th qtr 1981				1st qtr 1982 – 4th qtr 1982				1st qtr 1983 – 4th qtr 1983				1st qtr 1984 – 4th qtr 1984				1st qtr 1985 – 4th qtr 1985
Diagnosis/biopsy		5/80
Surgery		5/80
Radiation
Chemotherapy
IAT			7/80																7/84
CAM other
Imaging CXR		4/80
Imaging tomogram		4/80
Imaging CT scan abdomen		4/80
Imaging liver spleen scan		4/80
Imaging bone scan		5/80

Date	Description of Events	Requested	Status of requests
4/11/80	IVP of GU tract: within normal limits
4/12/80	IV cholangiogram: within normal limits
4/12/80	UGI with SBF: within normal limits
4/14/80	Barium enema: within normal limits
4/16/80	CT scan of abdomen: within normal limits
4/20/80	X-ray chest: collapse of portion LLL, air containing structure posterior to sternum; nodular density adj. to left hilum
4/22/80	Tomogram of left lung: possible mass adjacent to hilum is “distorted branch of pulmonary artery”
5/8/80	Exploratory laparoscopy, excision of multiple cysts, subtotal omentectomy for palliative: most of peritoneal cavity lined with cysts. Debulking done. Tumor is cystic, grape-like, no ascites.
5/8/80	Pathology of cysts on peritoneum: mesothelioma of peritoneum, multiple sites	Slides	Not avail.
5/10/80	X-ray chest: left ventricular enlargement
5/16/80	Tomogram of chest: volume loss LLL, unknown etiology
5/16/80	Bone scan of total body: within normal limits
5/17/80	Liver and spleen scan: within normal limits
6/25/80	Pathology: electron microscopy: multiple cystic mesothelioma of peritoneum
7/22/80–7/20/84	IAT 16 courses

Patient #1-19 Sigmoid Carcinoma (Dukes Stage C2)

Case 1-19

The patient in case 1-19 is a 50-year-old male with a family history of colon cancer. He was diagnosed with sigmoid carcinoma (Dukes stage C2) in March1985 after presenting with hematochezia, lower-left quadrant abdominal pain, and a normal CEA. Biopsies obtained during colonoscopy verified the diagnosis. He underwent a sigmoid resection, and 6 of 14 nodes were positive for metastases, but no gross residual disease was left in the abdomen. No other conventional therapy was pursued. He started IAT on 5/85 and completed 11 courses by 5/91. Serial colonoscopies have remained normal, with the last exam conducted on 9/8/00. At the last contact (interview, 10/12/01), the patient reported that his overall physical condition was excellent.

Pathology

3/18/85	Biopsy: mucinous producing adenocarcinoma, mod well diff, associated with adenomatous polyp, sigmoid colon, 6/14 nodes positive for mets, mesocolon and mesentery of colon.
9/8/00	Biopsy: colon polyp: no evidence of malignancy

Imaging

3/22/85	Liver spleen scan: normal
1/8/1987	CT abdomen pelvis: no evidence of recurrent tumor
3/27/87	Sigmoidoscopy: normal to 25cm
9/26/88	Colonoscopy: colon fully visualized to the cecum
4/13/89	CT scan abdomen; normal exam, no change compared with 1/8/87
10/5/89	Colonoscopy: normal exam
11/13/92	Colonoscopy: no evidence of recurrent colorectal polyps or cancer
12/2/94	Colonoscopy: normal exam
2/10/98	Sigmoidoscopy: normal to 40cm, normal anastamosis
5/7/98	Colonoscopy: normal exam
7/27/99	Sigmoidoscopy: normal to 70cm
9/8/00	Colonoscopy: sessile polyp (3mm) near anastamotic site

Tumor markers

3/17/85	CEAa <1.0 (normal)
2/25/86	CEA <2.5 (normal)
7/8/1986	CEA 1.9 (normal<2.5)
2/1/1987	CEA 1.8 (normal)
7/14/87	CEA 1.1 (normal <2.5)
3/9/88	CEA 1.9 (normal<2.5)
4/24/89	CEA 1.2 (normal)
10/4/89	CEA 2.0 (normal)
9/26/90	CEA 1.4 (normal)

a

Carcinoembryonic Antigen.

Conventional therapy

3/18/85

Surgery: sigmoid resection

Complementary therapy

5/21/85–5/7/91

IAT 11 courses

Patient # 1-19
EVENT	PERIOD 1				PERIOD 2				PERIOD 3				PERIOD 4				PERIOD 5				PERIOD 6				PERIOD 7				PERIOD 8				PERIOD 9				PERIOD 10				PERIOD 11				PERIOD 12
	1st qtr 1985 – 4th qtr 1985				1st qtr 1986 – 4th qtr 1986				1st qtr 1987 – 4th qtr 1987				1st qtr 1988 – 4th qtr 1988				1st qtr 1989 – 4th qtr 1989				1st qtr 1990 – 4th qtr 1990				1st qtr 1991– 4th qtr 1991				1st qtr 1992 – 4th qtr 1992				1st qtr 1994 – 4th qtr 1994				1st qtr 1998 – 4th qtr 1998				1st qtr 1999 – 4th qtr 1999				1st qtr 2000 – 4th qtr 2000
Diagnosis/biopsy	3/85																						9/90
Surgery	3/85
Radiation
Chemotherapy
IAT		5/85																								5/91
CAM other
Imaging CT scan									1/87									4/89
Colonoscopy															9/88					10/89												11/92				12/94		5/98									9/00
Sigmoidoscopy									3/87																												2/98						7/99
Tumor markers	3/85				2/86		7/86		2/87		7/87		3/88					4/89		10/89			9/90
Liver spleen scan	3/85

Date	Description of Events	Requested	Status of requests
	Family history of colon cancer in uncle
3/17/85	CEA <1.0 (normal)
3/18/85	Biopsy: mucinous producing adenocarcinoma, mod well diff, associated with adenomatous polyp, sigmoid colon, 6/14 nodes positive for mets, mesocolon and mesentery of colon.	Slides	Rcvd.
3/18/85	Surgery: sigmoid resection	Oper. Rpt.	Not avail.
3/22/85	Liver spleen scan: normal
5/21/85–5/7/91	IAT 11 courses
2/25/86	CEA <2.5 (normal)
7/8/86	CEA 1.9 (normal<2.5)
1/8/87	CT abdomen pelvis: no evidence of recurrent tumor	Films	Not avail.
2/1/87	CEA 1.8 (normal)
3/27/87	Sigmoidoscopy: normal to 25cm
7/14/87	CEA 1.1 (normal <2.5)
3/9/88	CEA 1.9 (normal<2.5)
9/26/88	Colonoscopy: colon fully visualized to the cecum
4/13/89	CT scan abdomen; normal exam, no change compared with 1/8/87	Films	Not avail.
4/24/89	CEA 1.2 (normal)
10/4/89	CEA 2.0 (normal)
10/5/89	Colonoscopy: normal exam
9/26/90	CEA 1.4 (normal)
11/13/92	Colonoscopy: no evidence of recurrent colorectal polyps or cancer
12/2/94	Colonoscopy: normal exam
2/10/98	Sigmoidoscopy: normal to 40cm, normal anastamosis
5/7/98	Colonoscopy: normal exam
7/27/99	Sigmoidoscopy: normal to 70cm
9/8/00	Colonoscopy: sessile polyp (3mm) near anastamotic site
9/8/00	Biopsy: colon polyp: no evidence of malignancy	Slides	Rcvd.

Patient #1-22 Squamous Cell Carcinoma of the Tongue

Case 1-22

The patient in case 1-22 is an 80-year-old male who was diagnosed in February 1999 with squamous cell carcinoma of the tongue accompanied by a benign parotid cyst. He subsequently completed the recommended course of radiation. Definitive surgery was recommended, but the patient refused, due to personal preference. IAT was initiated in June 1999, and he continues on maintenance therapy today. An MRI in October 2001 revealed no evidence of a discrete mass in the oropharynx and a decrease in right cervical lymph node. At the last contact (interview, 9/26/01), the patient reports that his overall physical condition is good.

Pathology

2/12/99	Biopsy left side tongue: squamous cell carcinoma, invasive, moderately differentiated
2/18/99	Biopsy (fine needle) right parotid lymph node: cystic contents; inconclusive
4/20/99	Biopsy (fine needle) right parotid lymph node: abscess with Strep species, acute suppurative inflammation with cocci
5/6/99	Biopsy aspiration of cyst in right parotid lymph node: cyst contents; acute inflammation

Imaging

2/17/99	CT scan left neck and tongue: invasive carcinoma of tongue extends to tonsillar fossa, parapharyngeal space, and beyond inferior margin of mandible into cervical subcutaneous tissue: large contralateral node metastasis
2/25/99	MRI of neck: ill-defined enhancing mass at base of tongue with extension into left piriformis sinus, highly suspicious for squamous cell carcinoma; cystic structure in submandibular space/ jugulodiagastric space
3/4/99	MRI neck: 2.26cm × 3.60cm × 3.50cm enhancing mass base of left tongue extending into hypopharynx, to level of epiglottis piriformis sinus; no extension past midline; cystic structure 3.2cm × 6.5cm × 7.80cm in jugulodiagastric region
12/8/99	CT scan neck: Resolution of left tongue base/lateral pharyngeal mass; pleomorphic adenoma or necrotic lymph node (right parotid cystic mass)
4/7/00	X-ray chest: emphysematous changes, otherwise normal
4/7/00	MRI of brain: normal
6/14/00	CT scan abdomen: bilateral lower lobe fibrosis consistent with UIP; possible nephrolithiasis involving left kidney
7/11/00	CT scan thorax: linear interstitial fibrosis consistent with UIP; bilateral apical fibrosis
7/23/00	CT scan neck: low attenuation of lesion on along right anterior border of right parotid gland; 2.2cm × 2.3cm; suspicious for metastatic necrotic lymph node
10/3/01	CT scan chest: bilateral interstitial lung disease
10/3/01	MRI neck: no evidence of discrete mass in oropharynx or oral cavity. Diffuse enhancement in dorsal aspect of hypopharynx could represent post-radiation changes. Interval decrease in right lymph node now measures 1.2cm

Conventional therapy

3/5/99–4/15/99

Radiation: upper neck, total rads 7200: 30 fractions over 41 days: completed full course: residual disease present after radiation

Complementary therapy

6/22/99-present

IAT (5 courses); still on maintenance therapy

Patient # 1-22
	PERIOD 1				PERIOD 2				PERIOD 3
EVENT	1st qtr 1999 – 4th qtr 1999				1st qtr 2000 – 4th qtr 2000				1st qtr 2001 – 4th qtr 2001
Diagnosis/biopsy	2/99, 2/99	4/99, 5/99
Surgery
Radiation		3/99
Chemotherapy
IAT			6/99
CAM other
Imaging CT scan	2/99			12/99			6/00, 7/00					10/01
Imaging CXR
Imaging MRI	2/99, 3/99	4/99										10/01

Date	Description of Events	Requested	Status of requests
2/12/99	Biopsy left side tongue: squamous cell carcinoma, invasive, moderately differentiated	Slides	Pend.
2/17/99	CT scan left neck and tongue: invasive carcinoma of tongue extends to tonsillar fossa, parapharyngeal space, and beyond inferior margin of mandible into cervical subcutaneous tissue: large contralateral node	Films	Pend.
2/18/99	Biopsy (fine needle) right parotid lymph node: cystic contents; inconclusive
2/25/99	MRI of neck: ill-defined enhancing mass at base of tongue with extension into left piriformis sinus, highly suspicious for squamous cell carcinoma; cystic structure in submandibular space/ juglodiagastric space
2/25/99	MRI of brain: normal
3/4/99	MRI neck: 2.26cm × 3.60cm × 3.50cm enhancing mass base of left tongue extending into hypopharynx, to level of epiglottis piriformis sinus; no extension past midline; cystic structure 3.2cm × 6.5cm × 7.80cm in juglodiagastric region
2/18/99	Definitive surgery recommended: patient refused
3/4/99	MRI neck: 2.26cm × 3.60cm × 3.50cm enhancing mass base of left tongue extending into hypopharynx, to level of epiglottis piriformis sinus; no extension past midline; cystic structure 3.2cm × 6.5cm × 7.80cm in
4/20/99	Biopsy (fine needle) right parotid lymph node: abscess with Strep species, acute suppurative inflammation with cocci
5/6/99	Biopsy aspiration of cyst in right parotid lymph node: cyst contents; acute inflammation
3/5/99–4/15/99	Radiation: upper neck total rads 7200: 30 fractions over 41 days: completed full course: residual disease present after radiation	Rpt. After treatment	Pend.
12/8/99	CT scan neck: Resolution of left tongue base/lateral pharyngeal mass.pleomorphic adenoma or necrotic lymph node (right parotid cystic mass)	Films	Pend.
4/7/00	X-ray chest: emphysematous changes, otherwise normal
4/7/00	MRI of brain: normal
6/14/00	CT scan abdomen: bilateral lower lobe fibrosis consistent with UIP; possible nephroliathiasis involving left kidney
7/11/00	CT scan thorax: linear interstitial fibrosis consistent with UIP; bilat apical fibrosis
7/23/00	CT scan neck: low attenuation of lesion on along right anterior border of right parotid gland; 2.2cm × 2.3cm; suspicious for metastatic necrotic lymph node
10/3/01	CT scan chest: bilateral interstitial lung disease	Films	Pend.
10/3/01	MRI neck: no evidence of discrete mass in oropharynx or oral cavity. Diffuse enhancement in dorsal aspect of hypopharynx could represent post-radiation changes. Interval decrease in right lymph node now measures 1.2cm	Films	Pend.

Patient #2-10 Pancreatic Cancer Involving the Bile Duct

Case 2-10

The patient in case 2-10 was a 55 year-old female with pancreatic cancer involving the bile duct. Her diagnosis was made in July 1999, after presenting with low back pain and a gastrointestinal bleed. No conventional therapy was pursued, as she was considered terminally ill at the time of her diagnosis and palliative drainage. Naltrexone was initiated on 11/11/99, and by July 2000, a CT scan showed a 90% reduction of her tumor mass. On August 8, 2000, she died from overwhelming septicemia, after three episodes of gram-negative sepsis secondary to loosening of her biliary stent. According to next of kin, no autopsy was performed.

Pathology

7/1/99

Biopsy of body of pancreas; carcinoma of pancreas (per physician's notes)

Imaging

Jul-00

CT scan abdomen: residual pancreatic lesions <1cm: 90% reduction of tumor mass; per physician's notes

Liver enzymes

10/22/99	Alk Phos- 1646; ALT 93; AST 159
10/23/99	Alk Phos- 1471; ALT 74; AST 108
11/21/99	Alk Phos- 2262; ALT 126; AST 180

Conventional therapy

7/1/99	Laparoscopy
Dec-99	Metenkephalin IV

Complementary therapy

11/11/99

Naltrexone 3mg qHS

Outcome

8/5/00

Death—due to septicemia secondary to loosened stent in bile duct

Patient # 2-10
	PERIOD 1				PERIOD 2
EVENT	1st qtr 1999 – 4th qtr 1999				1st qtr 2000 – 4th qtr 2000
Biopsy/diagnosis		7/99
Surgery		7/99
Radiation
Chemotherapy
Naltrexone
Imaging CT scan							7/00
Liver enzymes				10/99, 10/99, 11/99
Death							8/00

Date	Description of Events	Requested	Status of requests
7/1/99	Laparoscopy; diagnosis of pancreatic cancer per physician's notes	Slides	Pend.
10/22/99	Alk Phos- 1646; ALT 93; AST 159
10/23/99	Alk Phos- 1471; ALT 74; AST 108
11/21/99	Alk Phos- 2262; ALT 126; AST 180
11/11/99	Naltrexone 3mg qHS
Dec-99	Metenkephalin IV
Jul-00	CT scan abdomen: residual pancreatic lesions <1cm: 90% reduction of tumor mass; per physician's notes	Films	Pend.
8/5/00	Death--due to septecemia secondary to loosened stent in bile duct

Patient #2-21 Melanoma

Case 2-21

The patient in case 2-21 is a 67-year-old male who was diagnosed with melanoma in July 1996. The melanoma was resected from his right shoulder at that time, and no further therapy, other than close surveillance, was recommended. In April 1998, a lymph node dissection of his right axilla revealed metastatic disease in 1 of 15 lymph nodes. No conventional therapy was pursued. After presenting in August 1999 with proprioceptive changes in his left lower extremity, he had an MRI that showed a small brain lesion. This proved in fact to be a small bleed. During the course of 1999, the patient reported trying but not sustaining treatment with a variety of alternative therapies (see below). Also, he reported participating in a vaccine trial. Naltrexone was initiated in January 2000. At the last contact (interview, 10/10/2000), the patient reported that his overall physical condition was very good.

Pathology

7/23/96	Pathology from excision: malignant melanoma focally filling to papillary dermis (level III), vertical thickness 0.78mm. No abnormal melanocytes at margins of specimen
9/10/99	Biopsy brain: revealed no evidence of malignancy (per patient report)

Imaging

4/15/98	CT scan brain, chest, abdomen, and pelvis: no evidence of metastasis
8/1/99	MRI brain: proprioceptive changes in left lower calf and foot: diagnosed with cranial metastasis (per patient report) (this proved to be incorrect as the patient was later diagnosed to have had a small bleed

Conventional therapy

7/23/96	Surgical excision of pigmented skin lesion on right shoulder
8/13/96	Surgical excision after melanoma diagnosis confirmed
4/1/98	Surgery: lymph nodes: 1 of 15 nodes positive for malignancy
1999	Clinical trial: vaccinia melanoma cell lysates (VMCL) (per patient report)

Complementary therapy

1/00-present	Started Naltrexone 4.5mg
1999	Melatonin 3mg q.d. MVI q.d.; antioxidant q.d.; green tea; ginseng; vegetarian diet; selenium; milk thistle; pancreatic enzymes

Patient # 2-21
EVENT	PERIOD 1				PERIOD 2				PERIOD 3				PERIOD 4				PERIOD 5				PERIOD 6
	1st qtr 1996 – 4th qtr 1996				1st qtr 1997 – 4th qtr 1997				1st qtr 1998 – 4th qtr 1998				1st qtr 1999 – 4th qtr 1999				1st qtr 2000 – 4th qtr 2000				1st qtr 2001 – 4th qtr 2001
Biopsy/diagnosis			7/96												9/99
Surgery				7/96, 8/96						4/98
Radiation
Chemotherapy
Clinical trial													1999
Naltrexone																	1/00
CAM other													1999
Imaging-MRI brain
Imaging-CT scan abdomen										4/98					8/99

Date	Description of Events	Requested	Status of requests
7/23/96	Surgical excision of pigmented skin lesion on right shoulder
7/23/96	Pathology from excision: malignant melanoma focally filling to papillary dermis (level III), vertical thickness 0.78mm. No abnormal melanocytes at margins of specimen	Slides	Pend.
8/13/96	Surgical excision after melanoma diagnosis confirmed
4/1/98	Melanoma metastasized to right axilla with lymph node involvement (per patient report)	Slides	Pend.
4/15/98	CT scan brain, chest, abdomen, and pelvis: no evidence of metastasis (per patient report)	Films	Pend.
4/1/98	Surgery: lymph nodes: 1 of 15 nodes positive for malignancy
year '99	melatonin 3mg qd; MVI qd; antioxidant qd; green tea; ginseng; vegetarian diet; selenium; milk thistle; pancreatic enzymes
year '99	Clinical trial: vacinia melanoma cell lysates(VMCL) (per patient report)
8/1/99	Proprioceptive changes in left lower calf and foot (per patient report)
8/1/99	MRI brain: diagnosed with cranial metastasis (per patient report)	Films	Pend.
9/10/99	Biopsy brain: revealed no evidence of malignancy (per patient report)
1/00-present	Started Naltrexone 4.5mg

Patient #2-22 Adenocarcinoma of the Endometrium With Extension into the Peritoneum

Case 2-22

The patient in case 2-22 is a 58-year-old female diagnosed in May 1998 with adenocarcinoma of the endometrium with extension into the peritoneum. She completed four cycles of chemotherapy with adriamycin, cytoxan, and cisplatin. After her initial round of chemotherapy, adriamycin was withheld due to an equivocal multigated radionuclide (MUGA) scan and a past history of pericarditis. A course of radiation was completed. A CT scan (1/22/99) after chemotherapy and radiation showed a decrease in the pelvic mass. In July 1999, she was diagnosed with a second primary malignancy, intraductal carcinoma of the right breast with negative axillary nodes. Subsequent CT scans of her thorax revealed bilateral pulmonary nodules consistent with metastatic disease. She was referred to a thoracic surgeon, but a biopsy was not performed because the procedure was felt to be too difficult. She initiated Naltrexone in January 2001. In March 2001, a CT scan showed fewer abdominal and intrathoracic nodules compared to 1/3/01. A subsequent CT scan in June 2001 revealed a further reduction in peritoneal carcinomatosis. Her oncologist continues to follow her with serial CT scans. Currently, she reports her overall condition over the past week as excellent.

Pathology

5/8/98	Biopsy endometrium: pathology- adenocarcinoma, endometroid moderately to well-differentiated with 33% invasion of the myometrium: extension into peritoneum and left pelvic sidewall
7/29/99	Biopsy breast (right) pathology intraductal carcinoma well differentiated

Imaging

10/30/98	CT scan 2.5cm mass in lymph nodes on left side of pelvis (MD's notes only-no full report)
1/22/99	CT scan abdomen and pelvis: improvement in pelvic mass
4/9/99	CT scan abdomen and pelvis: improvement in pelvic mass
5/10/00	CT scan chest, abdomen, and pelvis: no abdominal or pelvic lesion. No evidence of metastatic disease. 1cm inguinal node unchanged
8/2/00	CT scan chest compared to 5/10/00 upper lobe anterior segment nodule 10mm; 3 new nodules 5mm left apex, 5mm lingula, 7mm right middle lobe. Progression of metastatic disease
9/29/00	CT scan chest: no adenopathy (mediastinal)-multiple small nodules; no change c/w 8/2/00
11/9/00	CT scan chest, abdomen, and pelvis: bilateral pulmonary nodules some cavitated. New peritoneal carcinomatosis
3/14/01	CT scan chest, abdomen, and pelvis: compared to 1/3/01; abdominal and intrathoracic nodules decrease in number
6/11/01	CT scan chest, abdomen, and pelvis: compared to 3/14/01; no new adenopathy, interval decrease in peritoneal carcinomatosis. Small superior mediastinal lymph node unchanged

Conventional therapy

7/15/98–9/24/98	Chemotherapy: cisplatin and AC; adriamycin held due to equivocal MUGA scan; four cycles
11/9/98–12/24/98	Radiation: 5400 cGy to para-aortic lymph nodes; CT scan on 1/22/99 showed improvement of pelvic mass
9/1/1999	Surgery: lumpectomy with sentinel node dissection: 1.7cm with clear margins and lymph nodes: ER + PR positive

Complementary therapy

1/9/01

Naltrexone 4.5mg daily

Patient # 2-22
	PERIOD 1				PERIOD 2				PERIOD 3				PERIOD 4
EVENT	1st qtr 1998 – 4th qtr 1998				1st qtr 1999 – 4th qtr 1999				1st qtr 2000 – 4th qtr 2000				1st qtr 2001 – 4th qtr 2001
Diagnosis/biopsy		5/98					7/99
Surgery							9/99
Radiation				11/98–12/98
Chemotherapy		7/98	9/98
Naltrexone													1/01
CAM other
Imaging CXR
Imaging tomogram
Imaging CT scan				10/98	1/99	4/99				5/00	8/00. 9/00	11/00	3/01	6/01

Date	Description of Events	Requested	Status of Requests
5/8/98	Biopsy endometrium: pathology- adenocarcinoma, endometroid moderately to well-differentiated with 33% invasion of the myometrium: extension into peritoneum and left pelvic sidewall	Slides	Pend.
7/15/98–9/24/98	Chemotherapy: cisplatin and AC; adriamycin held due to equivocal MUGA scan
10/30/98	CT scan 2.5cm mass in lymph nodes on on left side of pelvis (MD's notes only--no full report)	Films	Pend.
11/9/98–12/24/98	Radiation: 5400 cGy to para-artic lymph nodes; CT scan on 1/22/99 showed improvement of pelvic mass
1/22/99	CT scan abdomen and pelvis: improvement in pelvic mass	Films	Pend.
4/9/99	CT scan abdomen and pelvis: improvement in pelvic mass	Films	Pend.
7/29/99	Biopsy breast (right) pathology intraductal carcinoma well differentiated	Slides	Pend.
9/1/99	Surgery: lumpectomy with sentinel node dissection: 1.7cm with clear margins and lymph nodes: ER + PR positive
5/10/00	CT scan chest, abdomen, and pelvis: no abdominal or pelvic lesion. No evidence of metastatic disease. 1cm inguinal node unchanged.	Films	Pend.
8/2/00	CT scan chest compared to 5/10/00 upper lobe anterior segment nodule 10mm; 3 new nodules 5mm left apex, 5mm lingula, 7mm right middle lobe. Progression of metastatic disease
9/29/00	CT chest: no adenopathy (mediastinal)-multiple small nodules; no change c/w 8/2/00
11/9/00	CT chest, abdomen, and pelvis: bilateral pulmonary nodules, some cavitated. New peritoneal carcinomatosis	Films	Pend.
1/9/01	Naltrexone 4.5mg daily
3/14/01	CT scan chest, abdomen, and pelvis: compared to 1/3/01; abdominal and intrathoracic nodules decrease in number	Films	Pend.
6/11/01	CT scan chest, abdomen, and pelvis: compared to 3/14/01; no new adenopathy, interval decrease in peritoneal carcinomatosis. Small superior mediastinal lymph node unchanged	Films	Pend.