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Spontaneous Remissions in CancerSpontaneous remission or regression of cancer is usually considered a temporary or permanent, partial or complete vanishment of some or all of the relevant parameters of an accurately diagnosed malignant disease without medical treatment, or with medical treatment that is deemed inadequate to have produced such a disappearance of the cancer (). Spontaneous remissions are estimated by most experts to be 1 in 60,000 to 1 in 100,000 cases, but may be as low as 1 in 140,000 (). There are thousands of journal articles indexed in MEDLINE for spontaneous regression of cancer. Spontaneous regression of malignancies has been reported in all types of human cancer. The largest number of cases has been in patients with neuroblastoma, renal cell carcinoma, malignant melanoma, leukemias and lymphomas (). Regression in epithelial skin tumors is common and it may be partial or complete (). Almost all of familial self-healing epitheliomas and keratoacanthomas totally regress. In 25% of melanomas and 50% of basal cell carcinomas there is histological evidence of partial regression, total regression percentages are unknown. According to one study, this regression is associated with activated CD4 T cells, and perhaps is mediated by cytokines (). The most likely process causing spontaneous remissions is thought to be immune modulation, induction and inhibition of malignant protein expression and damaged gene repair. Clinical observations and laboratory evidence support this and other mechanisms to a variable degree. Mechanisms that have been proposed include ():
Some of these proposed mechanisms have been evaluated to the degree that they may be considered as part of a therapeutic regimen for cancer. For example, the Office of Complementary and Alternative Medicine of the National Institutes of Health has been examining the evidence that there may be an inverse correlation between the incidence of infectious diseases and cancer risk; and an inverse correlation between febrile infections and remissions of malignancies. The NIH published a meta-analytical review in 2002 in the Journal Neuroimmunomodulation. Their literature review found that the data indicates that the occurrence of fever in childhood or adulthood may protect against the later onset of malignancies and that spontaneous remissions of cancer are often preceded by fever inducing infections (). Indeed, folks who have never had a fever inducing infectious disease have been found in some studies to be 2.5 to 46.2 times more likely to have developed cancer than those who have had a febrile disease (). Also remarkable is a review that found 21 out of 353 people with a negative history of measles developed cancer vs. 1 out of 230 controls who had a positive history of measles (p<0.001) ().They further report that the use of whole body hyperthermia and use of fever-inducing substances have been administered successfully in palliative and curative treatments for metastatic cancer; one example is the use of fever induction under medical guidance for cancers of mesodermal origin (). Reports of spontaneous remissions are by their nature case reports, so they are err to the constraints of such studies. What follows is a representative sampling of the cases gleaned from the published scientific literature. A 61-year-old man was presented who had extensive metastases to his liver, abdominal wall, and lungs five years after pneumonectomy for poorly differentiated large cell and polymorphic lung cancer (). Histology of the primary was reviewed by several independent pathologists. There was radiological and clinical evidence for the lung and liver metastases, and a large metastatic mass of the abdominal wall was confirmed histologically. Remarkably, 8 months later, a surgeon who was operating for a correction of an inguinal hernia that had developed, was astounded to find that the large abdominal wall mass had completely disappeared. Five months later, there was no evidence of liver and lung metastases. By the time of the report in 1997, the remission had persisted for 5 years. Four cases of spontaneous remissions were reported by one author from his solo practice in 2002 (). These were:
Adult T-cell leukemia/lymphoma (ATL) is associated with HTLV-I virus, and the prognosis is generally poor. A case was reported of a 79-year-old woman who had spontaneous remission that was preceded by surgical biopsy and pneumonia (). Monoclonal HTLV-I proviral DNA detectable in her lymphocytes was undetectable after remission. She died two years later of pancreatic cancer while remaining in remission for ATL. Some cancers have an unpredictable course and chemotherapy for some patients can be quite risky. A case in point is congenital leukemia cutis. A case was presented of a new born who spontaneously remitted, and a link to withholding therapeutic interventions was propounded that encouraged withholding of therapy unless there was disease progression or an 11q23 translocation (). There are reports of other remissions with late relapses so a DNA test could be valuable in prognosis and guiding treatment. A report of the only verified case of spontaneous remission of lung cancer following a myxedema (low thyroid hormone) coma suggested that the regression might have been due to deprivation of thyroid hormone that induced total tumor apoptosis (). They suggest that hypothyroidism may increase the vulnerability of tumors to therapy induced or spontaneous regression by lowering the apoptotic threshold. Spontaneous remissions in breast cancer were researched in the international literature by a Danish team in 1999 (). They found 32 cases of spontaneous remission, and only 6 of these were adequately documented histologically. They also found in reports from the first part of the 20th century, that breast cancer has quite a variable natural course, and that a small percentage of women survive 10 to 15 years without treatment. Four cases were presented of long-term remission of malignant brain tumors following intracranial infections (). The authors reviewed the literature and suggested that although there may be direct oncolytic effects by bacteria, they believe that immune adjuvant responses to tumor suppression may have been at work. They observed that in one of the tumors where surgery was performed, the tumor tissue was infiltrated with many lymphocytes and granulocytes. In two of the other patients, tumor regression was associated with a bacterial infection that was not in contact with the tumor. And, in three of the patients, Enterobacter aerogenes was cultured. Although the presence of these bacteria may be coincidental, it is possible that an immunological cross-reaction to the tumor was elicited. From the laboratory, animal studies have identified a unique genetically determined, age dependent immune surveillance trait in a colony of mice that causes spontaneous regression of advanced cancer (). The tumor resistance appears to be a single-locus dominant trait that is effective against transplanted cells from cell lines of diverse types of cancer. Immediately after exposure or during spontaneous regression, a massive infiltration of leukocytes form aggregates or rosettes with the tumor cells, and rapidly and specifically lyses the tumor cells while not harming the host tissues. The mice then remain cancer-free. There is even one case study published in 2003 reporting the use of psychoneuroimmunological treatment of hepatocellular carcinoma in a women suffering from major depression (). Treatments consisted of psychotherapy, an antidepressant (fluvoxamine), glycyrrhizinic acid and dehydroepiandrosterone (DHEA). Liver function improved and alpha-fetoprotein levels normalized. Although spontaneous tumor regression is uncommon and the causes are unknown that they do occur has been well documented. There are probably important clues in those remissions that bear investigation and may lend themselves to new weapons in the fight against cancer. |
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