NCI Best Case Series Program

In 1990, the Office of Technology Assessment (OTA) conducted a formal review of the existing information on alternative cancer treatments (also called unconventional cancer therapies or UCTs) in response to a request by the US House of Representatives Committee on Energy and Commerce. [1] In response to the OTA’s recommendations, the NCI’s CTEP, Division of Cancer Treatment, Diagnosis and Centers (DCTDC) developed what would later be termed the NCI Best Case Series (BCS) Program. Because most alternative cancer treatments had not been formally evaluated in a prospective study, the NCI BCS Program was designed as a retrospective analysis of data of patients treated with an alternative cancer treatment to assess possible therapeutic benefit. [2]

Retrospective cases were solicited from practitioners through advertisement in complementary and alternative medicine journals. Cases that meet the NCI Best Case Series Program criteria were reviewed at the Office of Cancer Complementary and Alternative Medicine (OCCAM). Cases were evaluated by assessing the documentation of evidence for objective improvement in a patient’s tumor load while they received an alternative therapy. These patients had not received a conventional, or experimental, cancer therapy within the prior 4 weeks.

Cases that met the initial screening criteria were followed up with a request to review the pathology slides and radiographic images. Following review of pathology and radiology at the NIH, reviewers at OCCAM reassessed the cases for the second time. The cases that continued to meet eligibility criteria were sent to outside reviewers for their comments. These ad hoc reviewers include oncologists, basic scientists, and clinicians with expertise in clinical trials and early drug development.

The reviewers assessed the case reports and made comments about the strengths and weaknesses of each case.

The NCI Best Case Series Program started around 1991.The cancer therapy evaluation program (CTEP) ran the NCI Best Case Series Program until 1998. [3] Thirty-three case series representing 463 case reports were submitted between 1999 and 2010. Of these,14 case series representing 53 case report submissions were deemed to have sufficient information to be completed. Three CAM practices identified through the NCI Best Case Series were deemed appropriate to initiate NCI research. These therapeutic approaches were: 1) the treatment approach of the P. Banerji Homeopathic Research Foundation, 2) insulin potentiation therapy, and 3) macrobiotic lifestyle as per the Kushi Institute. The National Cancer Institute provided funds to conduct a prospective Practice Outcomes Monitoring and Evaluation System (POMES) study on the treatment approach of the P. Banerji Homeopathic Research Foundation after external review. The NCI IRB approved the study. However, the study was not done because of regulatory issues in India.

The NCI Best Case Series was converted to an IRB-reviewed protocol and approved in June 2011. Sixteen Case Series representing 220 cases were submitted for review and 58 cases met the eligibility criteria by May 2019. Of these, three case series were completed following submission. One intervention (a epigenetic therapy) went through the full review and was determined to warrant NCI-initiated research. A decision was made to implement pre-clinical studies as the next step to assessing the epigenetic therapy, however, these have not been conducted due to lack of funding.

Eligibility criteria

Inclusion criteria

• Diagnosis of cancer confirmed by histopathology or cytology.
• Documentation of detectable disease at the start of the alternative therapy.
• Appropriate blood tests, biomarkers, and/or bone marrow biopsy for hematological malignancies, indicating detectable disease
• No concurrent conventional treatment and at least 4 weeks from the last conventional treatment (e.g., chemotherapy, radiotherapy, hormonal therapy, or biologics).
• Patients or their legal guardian (for minors) must be able to give informed consent.
• All ages included

Exclusion criteria

• Patients with no detectable disease after surgery or conventional chemotherapy.
• Patients who are receiving concurrent or have received recent (< 4 weeks) conventional treatment for their cancer (e.g., chemotherapy, radiotherapy, hormonal therapy, or other biologics).

Objectives

The primary objectives of the NCI Best Case Series Program are to:

1. Verify the pathological diagnosis of cancer of the subjects in the retrospective cases.
2. Verify the presence and changes of abnormalities noted on medical imaging and hematological parameters of the subjects in the retrospective cases during the time of alternative cancer treatment.
3. Verify the medical histories of the subjects in the retrospective cases to confirm that they took the alternative treatment, and it was not given either concurrently or less than 4 weeks from other conventional treatments of known therapeutic potential.

The secondary objectives of the NCI Best Case Series Program are to:

1. Verify the progression free survival time of individual subjects retrospectively.
2. Verify the overall survival time of individual subjects retrospectively.

The primary endpoint is to determine whether NCI-initiated research (pre-clinical or clinical) is warranted for a specific alternative medicine therapy/intervention documented in the case reports.

The goal of the NCI Best Case Series Program is to identify CAM interventions that warrant NCI initiated research.

The protocol is open only for the purpose of analyzing existing data, and NOT accepting new case series.