Metastatic Malignant Melanoma with Spontaneous and Complete Regression of the Primary Lesion

Shai, Ayelet; Avinoach, Ilana; Sagi, Amir

doi:10.1111/j.1524-4725.1994.tb01635.x

Cited by 28 publications

(18 citation statements)

References 25 publications

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“…Complete regression of melanoma has traditionally been defined as the absolute absence of any dermal or junctional melanocytes and replacement of the entire lesional area by varying amounts of fibrosis, inflammation, and sometimes abundant melanophages (tumoral melanosis) in the site of a previously documented pigmented lesion. 9,11 In such scenarios, since no melanocytes remain in the lesion, a definitive diagnosis of regressed melanoma cannot be rendered, but the optimal diagnosis would rather be 'pigment incontinence consistent with a completely regressed melanocytic lesion'. As such, the malignant biologic potential of the regressed lesion is realized only if the patient develops regional or distant metastasis.…”

Section: Heterogeneity In the Definition Of Histologic Regressionmentioning

confidence: 99%

Regression in primary cutaneous melanoma: etiopathogenesis and clinical significance

Aung

Nagarajan

Prieto

2017

Laboratory Investigation

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Though not required currently for staging, regression is a histopathologic parameter typically reported upon diagnosis of an invasive primary cutaneous melanoma. The studies examining the prognostic significance of regression in patient outcome have yielded controversial findings; likely because the definition and assessment of regression have not been consistent, in addition to subjectivity of pathologists' interpretation. Regression is histologically characterized by variable decrease in the number of melanoma cells accompanied by the presence of a host response consisting of dermal fibrosis, inflammatory infiltrate, melanophages, ectatic blood vessels, epidermal attenuation, and/or apoptosis of keratinocytes or melanocytes; the relative extent of these features depends on the stage of the regression. However, the magnitudes to which these individual changes must be present to meet the threshold of histologic regression have not been well defined or agreed upon, and thus, the definition and classification of histologic regression in melanoma varies considerably among institutions and even among individual pathologists. In order to determine the clinical significance of histologic analysis of regression, there is a compelling need for a universal scheme to objectively define and assess histologic regression in primary cutaneous melanoma, so that the biologic and prognostic significance of this process may be completely understood.

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Section: Heterogeneity In the Definition Of Histologic Regressionmentioning

confidence: 99%

Regression in primary cutaneous melanoma: etiopathogenesis and clinical significance

Aung

Nagarajan

Prieto

2017

Laboratory Investigation

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“…2 Complete regression of primary cutaneous malignant melanoma is a rarer occurrence, with only 34 well-documented cases in the MEDLINE-cited, English-language or English languageesummarized literature. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] We detail 4 additional cases of completely regressed primary cutaneous melanoma with nodal and/or regional metastases. These cases embody important information regarding tumor immunogenicity and escape from immunosurveillance.…”

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Completely regressed primary cutaneous malignant melanoma with nodal and/or visceral metastases: A report of 5 cases and assessment of the literature and diagnostic criteria

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Stewart²,

Wilbers

et al. 2005

Journal of the American Academy of Dermatology

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“…Such responses to placebo have led to the suggestion that a minimum response rate of 18% be required of an agent in phase II studies before proceeding to phase III studies (14). Pathologic assessment of melanoma specimens suggests some degree of remission in 10% to 36% of cases (15).…”

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Objective Responses in Patients with Malignant Melanoma or Renal Cell Cancer in Early Clinical Studies Do Not Predict Regulatory Approval

Goffin

Baral

et al. 2005

Clinical Cancer Research

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Purpose: Tumor responses in early-phase trials are used to determine whether new agents warrant further study. Given that spontaneous regressions are observed in melanoma and renal cell carcinoma, this study assessed whether tumor responses, particularly in these two tumor types, predict for future regulatory drug approval. Experimental Design: The literature was reviewed to assess tumor response rates to cytotoxic agents in phase I and II trials in the following solid tumors: melanoma, renal cell carcinoma, nonŝ mall-cell lung cancer, breast cancer, ovarian cancer, colorectal cancer, and other solid tumors.Response rates were categorized and the relationship of these categories to the end point of regulatory drug approval was determined.Results: Fifty-eight drugs were assessed in 100 phase I trials, and 46 of these drugs were also studied in 499 phase II trials. Higher overall response rates in both phase I trials (P = 0.03) and phase II trials (P < 0.0001) were predictive of regulatory approval. However, response in melanoma or renal cell carcinoma was not predictive for either phase I or phase II studies.Conclusions: For cytotoxic agents, although overall objective response rates reliably predict subsequent marketing approval, isolated responses in melanoma and renal cell carcinoma are not predictive.Contemporary drug development in oncology is extremely resource intensive. Only one in ten drugs that enter the clinic is eventually approved for use (1) and the dollar cost to bring a drug to market can approach U.S. $800 million (2). The human cost of late-phase development of inactive therapeutics is also considerable, and includes toxicity suffered by research subjects, unrealistic hope generated by seemingly promising new agents, and the wasted accrual of the limited pool of patients who are eligible for trials. Hundreds, or even thousands, of patients may be exposed to a new agent only to eventually determine that it does not provide clinical benefit, sometimes after completion of multiple phase III trials. Objective tumor response remains the most commonly used end point or surrogate of drug efficacy, and tumor response has been shown to correlate with survival (3 -6). In lung cancer, for example, a response rate of 15% is usually considered sufficient to merit further investigation of an agent (7).The decision whether to continue the development of a new therapeutic based on the results of early clinical trials (phase I or II) may be challenging, and is based on an evaluation of the therapeutic index. Whereas new therapeutics can be developed despite manageable toxicities, a critical consideration is the antitumor activity of the agent. Some clues can be gleaned from preclinical studies. have shown that preclinical data may predict for tumor responsiveness to cytotoxic agents in phase II studies. Measures of tumor control in in vitro human tumor cell line models, murine xenograft models, and murine tumor allograft models were compared with the phase II response rates in studies of non -small-cel...

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Metastatic Malignant Melanoma with Spontaneous and Complete Regression of the Primary Lesion

Abstract: Greater attention should be devoted to identification of regression in melanoma, clinically and histologically, evaluating the prognostic implications which regression might indicate.

Cited by 28 publications

References 25 publications

Regression in primary cutaneous melanoma: etiopathogenesis and clinical significance

Regression in primary cutaneous melanoma: etiopathogenesis and clinical significance

Completely regressed primary cutaneous malignant melanoma with nodal and/or visceral metastases: A report of 5 cases and assessment of the literature and diagnostic criteria

Objective Responses in Patients with Malignant Melanoma or Renal Cell Cancer in Early Clinical Studies Do Not Predict Regulatory Approval

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