ASO Author Reflections: Is There a Relationship Between TIL and Regression in Melanoma?

Annals of Surgical Oncology -     

A new approach to the therapy of cancer based on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2

A new approach to cancer therapy has been developed based on the adoptive transfer of autologous lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (IL-2). Forty-one patients with advanced cancer who have failed all standard treatments were treated in this experimental protocol. Fourteen patients experienced an objective regression of cancer, including one patient with metastatic melanoma who underwent a complete regression. Objective responses were seen in patients with colorectal cancer, renal cell cancer, melanoma, and lung adenocarcinoma. The sites of tumor regression included subcutaneous tissue, lung, and liver. The major side effect of therapy resulted from the administration of high-dose IL-2 and was manifested primarily as fluid retention, resulting in a generalized capillary permeability leak syndrome. This approach to adoptive immunotherapy represents a promising approach to the therapy of patients with metastatic cancer. Attempts to increase the potency and decrease the toxicity of therapy and extend this treatment to patients with smaller tumor burdens are in progress.     

Improved survival in young women with breast cancer

Background: Young age has been hypothesized to be an adverse prognostic factor for women with breast cancer. This association, based on historical data, may not reflect recent advances in breast cancer management. Methods: A retrospective study was conducted of all women age 30 or younger who underwent definitive operation at our institution for primary operable breast carcinoma during one of two consecutive 20-year periods (1950–1969 or 1970–1989). All cancers were restaged according to current staging criteria. Actuarial survival and recurrence-free survival rates from the two patient eras were compared with each other and with published statistics for older breast cancer patients. Results: Eligibility criteria were met by 81 women from the 1950–1969 era and 146 women from the 1970–1989 era. Histologic diagnoses, tumor sizes, incidence of axillary nodal metastases, number of positive nodes, and American Joint Committee on Cancer stage at presentation were similarly distributed in the two eras. Despite these similarities, improved survival (p=0.009) was observed in the later era. Local recurrences were also more common (p<0.05) in the later era in association with less extensive resections. These local recurrences had an adverse impact on recurrence-free survival in the later era, but no concomitant decrease in overall survival was observed. Node-positive patients who received chemotherapy demonstrated a trend toward improved survival (p=0.06) compared with node-positive patients who did not. Survival for patients in the later era was similar to that for older women as reported in other published series. Conclusions: The stage of presentation of breast cancer in women 30 years or younger appears unchanged from prior decades, but survival has improved in association with the use of less extensive surgical resections and the introduction of cytotoxic chemotherapy. With current treatment, primary operable breast cancer in young women appears to have a similar prognosis to breast cancer in older women.Results of this study were presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994, and was judged Best Clinical Paper in the Resident/Fellow Essay Contest.     

Synchronous colon primaries have the same prognosis as solitary colon cancers

PURPOSE: This study was designed to determine the prognosis of patients with synchronous colon primary tumors. METHODS: An 18-year, multi-institutional database of 4,878 colon cancer patients was reviewed, and patients with synchronous tumors were identified. Survival for each group was calculated by the Kaplan-Meier method and compared using log-rank analysis. RESULTS: There were 160 patients (3.3 percent) with 339 synchronous tumors. Eight percent of these patients had more than two tumors at the time of diagnosis. TNM staging of all synchronous tumors was 12 percent Stage 0, 41 percent Stage I, 21 percent Stage II, 16 percent Stage III, and 7 percent Stage IV. Based on highest stage lesion, 1 percent of patients were at Stage 0, 28 percent Stage I, 33 percent Stage II, 25 percent Stage III, and 11 percent Stage IV. Disease-specific five-year survival by highest stage was 87 percent for Stage O or I, 69 percent for Stage II, 50 percent for Stage III, and 14 percent for Stage IV (all differences significant by log-rank test). These highest stage survivals for patients with synchronous tumors were not significantly different from survival of patients with same stage solitary tumors in our database or from survival of patients with solitary colon cancer in national tumor databases. CONCLUSION: For patients with synchronous colon cancers, survival is the same as for patients with solitary colon tumors on a stage-for-stage basis, when highest stage synchronous tumor is considered.Read at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.     

Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses.

PURPOSE: To measure the CD8+ T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule. PATIENTS AND METHODS: Thirty HLA-A2-positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209-2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund's adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry. RESULTS: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CD8+ T cells specific for the g209-2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P <.0001). Eight patients (28%) exhibited peptide-specific CD8+ T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b-treated patients also had significant increases in tetramer-binding cells (P <.0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P =.59). CONCLUSION: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8+ T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results.     

Perforation of the colon in the immunocompromised patient

Perforation of the colon in the immunocompromised patient is a catastrophic and usually fatal event. The immunocompromised patient, like all patients, may suffer from the more common causes of colonic perforation, including diverticulitis, chronic inflammatory bowel disease, presence of a foreign body, and trauma. There also appears to be in these patients the unusual occurrence of spontaneous perforation, particularly in patients with renal allografts or on dialysis. In a retrospective multi-hospital review, 10 cases of apparent spontaneous perforation were found. The pathogenesis is unclear, but predisposing factors include immunosuppressive medications, uremia, discrete colon ulcerations, and fecal impaction. The reported mortality rate approaches 100 percent due to delayed recognition and impaired host defense mechanisms. In our patients, mortality was 40 percent. We attribute this improved survival to prompt surgical intervention and aggressive postoperative management, including daily dialysis, parenteral hyperalimentation, broad-spectrum antibiotics, and a high index of suspicion for ongoing sepsis with early repeat exploration.     

A new score for the evaluation of palpable breast masses in women under age 40

BACKGROUND: The purpose of this study was to develop a rapid and accurate diagnostic test for palpable breast masses in women under age 40. METHODS: Masses were evaluated utilitzing a modified triple test score (MTTS), which assigned scores of 1 point for benign, 2 points for suspicious, or 3 points for malignant findings from physical examination, ultrasonography, and fine needle aspiration. The MTTS was the sum of the three scores and was correlated with biopsy or follow-up. RESULTS: Among 113 masses, 100 scored 3 points, 8 scored 4 points; all were benign. Three scored 5 points; 1 was malignant. Two scored >or=6 points: both were malignant. CONCLUSIONS: The MTTS has 100% diagnostic accuracy when other than 5 points. Masses scoring or=6 points may proceed to definitive therapy. Masses scoring 5 points (3%) require biopsy. This approach avoids open biopsy in the majority of cases, while capturing all malignancies.     

Geographic variation in sentinel node adaptation by practicing surgeons in Oregon

BACKGROUND: The sentinel node biopsy (SNB) technique is an important tool in the diagnosis and treatment of breast cancer and melanoma. However, surgeons in Oregon have not universally adopted its use. METHODS: Mailed questionnaire. RESULTS: The response rate was 32%. Seventy-four (76%) of the surgical respondents perform routine SNB; 49% completed courses, and 32% learned the technique in residency. Sixty-one (89%) performed axillary dissection with their initial cases. It took 21 of 40 (52%) surgeons greater than a year to accrue 20 cases. Of 23 surgeons (24%) not performing SNB, 89% believed it was an important skill to obtain, and 70% thought they would benefit from proctoring opportunities. Six (26%) did not have technological support at their hospital. Surgeons at hospitals with less than 50 beds (P = .001) and at rural hospitals (P = .003) were less likely to perform SNB. CONCLUSION: The majority of urban general surgeons in Oregon use SNB in their practice. However, the incorporation of SNB for surgeons practicing in smaller hospitals and rural settings is less frequent than in the urban environment. As SNB becomes the standard of care, we need to overcome these barriers so that patients can have access to this procedure in their own communities.