Localized synchronous squamous cell carcinomas of the esophagus and hypopharynx treated with definitive concurrent chemoradiotherapy with a unified radiotherapy plan.

Because of common risk factors, synchronous squamous cell carcinomas of the esophagus and head and neck are common, and their concurrent presence can significantly complicate disease eradication and survival. Here, we report the case of a patient with a history of extensive tobacco and alcohol use who was diagnosed with a localized thoracic esophageal squamous cell carcinoma, and in whom positron-emission tomography-computed tomography discovered a nearby asymptomatic localized hypopharyngeal focus that was confirmed by biopsy to also be malignant. He was treated with definitive concurrent chemoradiotherapy in a single unified radiotherapy plan, with surgery reserved for salvage treatment. He currently remains in remission without a need for surgical salvage. However, significant concern remains for both treatment failure and development of another primary because of "field cancerization."

Complete 5-year follow-up of a prospective phase II trial of preoperative chemoradiotherapy for esophageal cancer.

BACKGROUND: Conclusive evidence supporting the routine use of multimodality therapy in esophageal cancer is lacking. However, since long-term survival after esophagectomy alone is unusual, clinical trials designed to identify effective therapeutic regimens are essential. We report here the 5-year results of a phase II induction chemoradiotherapy trial. METHODS: From August 1991 to January 1995, 44 patients with esophageal or gastroesophageal junction carcinoma were treated with a combination of 5-fluorouracil, cisplatin, and interferon-alpha with concurrent external beam radiotherapy. RESULTS: Forty-one (93%) patients completed chemoradiotherapy, with most toxic events recorded as grade I or II. Curative resection (all gross tumor removed) was achieved in 36 of 37 surgical explorations, with 10 tumors demonstrating complete pathologic response and 23 showing partial pathologic response. Median follow-up for survivors was 75 months (range, 60-100 months). Five-year survival for all patients was 32%, with a median survival of 28 months. Five-year disease-free survival in patients with curative resection was 36% (median, 26 months) and overall survival was 39% (median, 34 months). Five-year survival for patients with curative resection whose disease responded to chemoradiotherapy was 42% (median overall survival, 36 months). Local-regional recurrence alone occurred in 3 patients, distant failure alone in 12 patients, and combined local-regional and distant failure in 2 patients. A Cox proportional hazards model identified both pathologic tumor and nodal stage as independent predictors of disease-free survival. Fourteen patients (32%) were 5-year survivors; 1 of these patients later experienced disease recurrence and died. CONCLUSIONS: Preoperative chemoradiotherapy can result in a long-term and durable disease-free state. Only large, multi-institutional phase III trials can determine whether combined modality therapy is superior to resection alone.

Pancreatic cancer in a young adult after treatment for Hodgkin's disease.

The authors present a case of adenocarcinoma of the head of the pancreas, which arose 14 years after extended field irradiation for Stage IIA Hodgkin's disease. The patient was aged 37 years at the time of the pancreatic cancer, which was situated within the previously irradiated volume.

Angiosarcoma of the breast mimicking radiation dermatitis arising after lumpectomy and breast irradiation: a case report.

Angiosarcoma arising in the breast is a very rare malignancy. Of the small number of reported cases, most arose in the breast after breast irradiation. A case is reported of angiosarcoma arising in the breast more than 7 years after lumpectomy and breast irradiation for carcinoma of the breast. The initial appearance was very similar to the changes of late radiation dermatitis and the true nature of the malignant lesion was not known for 23 months.

Preoperative chemoradiotherapy for carcinoma of the esophagus and gastroesophageal junction.

PURPOSE: To determine whether combination 5-fluorouracil, cisplatin, and interferon alfa, an active regimen in advanced esophageal cancer, is efficacious as induction therapy before esophagectomy. MATERIALS AND METHODS: Forty-four patients with potentially resectable esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma were entered into a phase I/II study of this chemotherapeutic regimen and concurrent external-beam radiotherapy before resection. The initial 16 patients were treated with prolonged-infusion 5-fluorouracil (300 mg/m2 on days 1 to 28), cisplatin (20 mg/m2 on days 1 to 5 and 24 to 28), interferon alfa (3 x 10(6) U/m2 intravenously on days 1 to 5 and 24 to 28; subcutaneous injection every other day on days 6 to 23), and radiation (4000 cGy). The subsequent 28 patients were treated over 21 days with two modifications: dose escalation of 5-fluorouracil (250 to 350 mg/m2) and double-fractionated radiotherapy to a total dose of 4500 cGy. RESULTS: Forty-one patients completed chemoradiotherapy and were evaluable for toxicity. Adverse events were substantial but tolerable, and most toxic episodes were hematologic and gastrointestinal. Three patients died, and one patient had progressive disease before resection. Of the 37 patients eligible for curative resection, 36 had all gross tumor removed. Thirty-three (80%) patients had a major pathologic response: 10 (24%) with no residual tumor and 23 with only microscopic residual tumor. Median survival for all patients was 27 months and for responders was 36 months. CONCLUSIONS: This combination regimen is active but yields results similar to those of other chemoradiotherapy phase II trials; therefore, the contribution of interferon alfa to treatment efficacy remains uncertain. The true worth of preoperative chemoradiotherapy is unknown pending results of phase III trials.

Ductal carcinoma in situ (DCIS) of the male breast treated by lumpectomy and breast irradiation.

A male patient with ductal carcinoma in situ (DCIS) of the breast, treated with lumpectomy and postoperative breast irradiation, is presented. Because of associated obesity, the patient felt that mastectomy would leave him with a noticeable cosmetically unacceptable deformity. Radiotherapy was administered using the exact techniques used to treat the female breast. At 44 months following completion of radiotherapy, the patient is free of disease and has an excellent cosmetic result. Thus, if there are compelling reasons to avoid mastectomy in a male patient, lumpectomy and breast irradiation should be considered as a reasonable alternative for treatment of DCIS.

Erythropoietin increases the radioresistance of a clonal hematopoietic progenitor cell line expressing a transgene for the erythropoietin receptor.

Erythropoietin (Epo) is a serum glycoprotein growth factor required for the survival, proliferation and differentiation of committed erythroid progenitor cells. In the present study, we sought to determine whether the action of Epo via its receptor is also implicated in the repair of radiation-induced cell damage. Overexpression of the Epo receptor (Epo-R) was achieved as a result of transfection of the 32D cl 3 clonal hematopoietic cell line. These clonal lines allowed us to investigate the effects of Epo on the radiation sensitivity in vitro of a clonal murine hematopoietic progenitor cell line. Low level expression of Epo-R on many hematopoietic cell types was thus circumvented. Ligand binding of Epo resulted in increased radioresistance of 32D cl 3 subclonal lines expressing the Epo-R transgene. The D0 of 32D Epo-R cells at 1.49 Gy/min was 1.33 Gy and n was 1.39. The D0 of parental clonal cell line 32D cl 3 cells at 1.49 Gy/min was 1.36 Gy and n was 1.39. In contrast, at the low dose rate of 0.0595 Gy/min, the D0 of 32D Epo-R cells was 2.0 Gy and n was 1.24, while parental clonal line 32D cl 3 showed a D0 of 1.35 Gy and n was 1.39. The increased radioresistance was statistically significant at low dose rate (p < 0.05). Combined exposure to Epo and interleukin 3 (IL-3) increased proliferation of 32D Epo-R cells but did not induce a detectable further increase in radioresistance. Temporal dissociation between growth factor-activated tyrosine phosphorylation of intracellular substrates, and the radioprotective effect was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of T-cell growth factors (interleukins 2, 4, 7, 10, and 12) in the evaluation of T-cell reactivity to melanoma.

Melanoma represents the single best example of a human tumor that has been shown to elicit specific T-cell reactivity. The responsiveness of some patients with metastatic melanoma to treatment with the prototypic T-cell growth factor (TCGF), interleukin-2 (IL-2), indicates that T cells play a role in antitumor immunity. Interleukin-4 (IL-4), another TCGF that has been administered clinically to humans, was not associated with tumor response in our trials conducted at the Surgery Branch of the National Cancer Institute. Combination trials of IL-2 with IL-4 have shown no increase in responsiveness of melanoma or other tumors when compared to IL-2 alone. However, enhanced expansion of tumor-infiltrating lymphocytes (TILs) in vitro has been observed with combinations of low-dose IL-2 and IL-4. We have begun a study evaluating the trafficking of such expanded lymphocytes following their adoptive transfer in association with systemic administration of IL-2 and IL-4. We have established several TIL cultures from fresh tumor samples, maintained them in long-term culture, and marked them with the neomycin phosphotransferase gene using the LNL6 retroviral vector. Such TILs appear to demonstrate no notable alterations in phenotype or cytolytic activity when compared to their nontransduced counterparts. In addition to IL-2 and IL-4, there are a variety of other novel TCGFs that are now available for evaluation in preclinical and clinical trials. IL-7 induces proliferation and lymphokine-activated killer (LAK) cell activity from human peripheral blood mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Twice daily thoracic irradiation for limited small cell lung cancer.

Thoracic failure is a significant obstacle to the cure of limited stage small-cell lung cancer (LSCLC) patients treated with combined modality therapy. In 1985 we initiated a prospective trial to evaluate the impact of twice daily thoracic irradiation without concomitant chemotherapy on control of intrathoracic tumor in LSCLC. Twenty-nine patients treated in this fashion were compared with 36 patients treated from 1979-1982 with once daily thoracic irradiation and concomitant chemotherapy. Both groups received the same induction chemotherapy; cyclophosphamide, Adriamycin, and vincristine (CAV) alternating with cisplatin and etoposide. For consolidation, the twice daily patients received thoracic irradiation, 45 Gy in 1.5 Gy fractions given twice daily, and the once daily patients received thoracic irradiation, 45 Gy in 2.5 Gy fractions given once daily with concomitant cyclophosphamide and vincristine. After completion of radiotherapy both groups received maintenance chemotherapy. The complete response (CR) rate after thoracic irradiation was higher for twice daily patients (86% (25/29) compared to the once daily patients [61% (22/36), p = 0.02]. However, this advantage was offset by the shorter duration of thoracic control among CR patients treated with twice daily thoracic irradiation compared to once daily thoracic irradiation (32% vs 67% at 2 years, p less than 0.05). In view of the enhanced initial response of LSCLC to twice daily thoracic irradiation, this basic radiotherapeutic approach seems appropriate, but new strategies using higher doses of twice daily thoracic irradiation or concomitant chemotherapy appear to be necessary to enhance long-term thoracic control.

Limited small cell lung cancer: prognostic significance of a complete response to the induction phase of chemotherapy followed by thoracic irradiation.

Limited-stage small cell lung cancer is frequently treated with induction combination chemotherapy (ICC), followed by consolidation with thoracic irradiation. It has been suggested that patients who do not have a complete response to ICC are unlikely to have control of occult distant metastasis and consequently have such a poor prognosis that thoracic irradiation is unlikely to be of benefit. To examine this hypothesis, 48 patients treated on prospective protocols who achieved a complete response to ICC or subsequently to thoracic irradiation were analyzed. Twenty-four patients had a complete response to ICC (CR-ICC), and 24 subsequently converted to complete-response status after thoracic irradiation (CR-TI). The two groups had similar prognostic factors and treatment. Comparing CR-ICC and CR-TI patients, survival was 40% versus 26% at 2 years and 35% versus 4% at 5 years, respectively (P less than .05). Freedom from distant metastasis was 41% at 5 years for the CR-ICC patients and 8% for the CR-TI patients (P less than .05). A modest number of CR-TI patients were long-term survivors, suggesting a value for thoracic irradiation as consolidation therapy.