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Radiotherapy-related dermatological toxicities over time have not been well quantified. We examined during and immediately following radiation therapy skin toxicities over time in a randomized study of mometasone furoate vs placebo during breast radiotherapy. Patients with breast cancer undergoing radiotherapy to the breast or chest wall were randomized. Symptoms related to skin toxicity were addressed weekly using provider-reported Common Terminology Criteria for Adverse Events (CTCAE v3.0) and 4 patient-reported outcomes (PRO) surveys. We applied repeated measures and risk analysis methodologies. One hundred seventy-six patients were enrolled. By CTCAE, significant differences favoring mometasone were detected over time in all toxicities except skin striae, atrophy, and infection. Statistically significant differences between arms at baseline but not over time occurred for all Linear Analog Self-Assessment. Statistically significant differences occurred for all symptoms in the temporal profile of symptoms as measured by PRO surveys (all P

Purpose The Head and Neck Intergroup conducted a Phase III randomized trial to determine whether the addition weekly cisplatin to daily radiation therapy (RT) would improve survival in patients with unresectable squamous cell head-and-neck carcinoma. Methods and Materials Eligible patients were randomized to RT (70 Gy at 1.8–2 Gy/day) or to the identical RT with weekly cisplatin dosed at 20 mg/m 2 . Failure-free survival (FFS) and overall survival (OS) curves were estimated with the Kaplan-Meier method and compared with the log rank test. Results Between 1982 and 1987, 371 patients were accrued, and 308 patients were found eligible for analysis. Median follow-up was 62 months. The median FFS was 6.5 and 7.2 months for the RT and RT + cisplatin groups, respectively ( p = 0.30). The p value for the treatment difference was p = 0.096 in multivariate modeling of FFS (compared to a p = 0.30 in univariate analysis). Expected acute toxicities were significantly increased with the addition of cisplatin except for in-field RT toxicities. Late toxicities were not significantly different except for significantly more esophageal (9% vs. 3%, p = 0.03) and laryngeal (11% vs. 4%, p = 0.05) late toxicities in the RT + cisplatin group. Conclusion The addition of concurrent weekly cisplatin at 20 mg/m 2 to daily radiation did not improve survival, although there was evidence of activity. Low-dose weekly cisplatin seems to have modest tumor radiosensitization but can increase the risk of late swallowing complications.

Purpose: The purpose of this study was to determine whether or not for patients with squamous cell carcinomas of the head and neck, a surgical resection leaving positive margins followed by postoperative adjuvant therapy improves the outcome compared to a matched group of patients treated with definitive radiotherapy alone. Methods and Materials: From January 1985 through January 1990 a consortium of national cooperative groups (Radiation Therapy Oncology Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Northern California Oncology Group, Southeast Group, and Southwest Oncology Group) conducted a phase III clinical trial testing the efficacy of adjuvant chemotherapy for patients with resectable, squamous cell carcinomas of the head and neck. One hundred and nine patients were excluded from this study due to positive surgical margins. These patients have been followed prospectively with regards to local/regional tumor control, development of distant metastases, and survival. The postoperative treatment of these patients was not specified by the protocol but the majority of patients received postoperative radiotherapy ± chemotherapy. These patients were compared with a matched group of patients from the Radiation Therapy Oncology Group head and neck database of patients treated with definitive radiotherapy alone using a standard fractionation schema. Matching parameters included primary tumor site, T -stage, N -stage, Karnofsky performance status, and age. Results: Actuarial curves are presented for local/regional control and survival. At 4 years the local/regional control rate is 44% for the positive margin patients compared to 24% for the patients from the data base ( p = 0.007). However, there is no significant difference between the survival curves ( p = 0.76) with respective median survivals being 18.1 months vs. 17.9 months and 4-year survivals being 29% vs. 25%. Conclusion: While an incomplete excision followed by postoperative therapy does not seem to improve survival compared to treatment with radiotherapy alone, it appears to yield significantly better local/regional control. This would argue for its applicability in selected palliative settings. A follow-up, Phase III trial for patients with advanced tumors may be warranted to test traditional resectability criteria.

To test the efficacy of sequential chemotherapy as an adjuvant to surgery and postoperative radiotherapy for patients with locally-advanced but operable squamous cell cancers of the head and neck region, a randomized clinical trial was conducted under the auspices of the Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeast Group). Eligible patients had completely resected tumors of the oral cavity, oropharynx, hypopharynx, or larynx. They were then randomized to receive either three cycles of cis-platinum and 5-FU chemotherapy followed by postoperative radiotherapy (CT/RT) or postoperative radiotherapy alone (RT). Patients were categorized as having either "low-risk" or "high-risk" treatment volumes depending on whether the surgical margin was greater than or equal to 5 mm, there was extracapsular nodal extension, and/or there was carcinoma-in-situ at the surgical margins. Radiation doses of 50-54 Gy were given to "low-risk" volumes and 60 Gy were given to "high-risk" volumes. A total of 442 analyzable patients were entered into this study with the mean-time-at-risk being 45.7 months at the time of the present analysis. The 4-year actuarial survival rate was 44% on the RT arm and 48% on the CT/RT arm (p = n.s.). Disease-free survival at 4 years was 38% on the RT arm compared to 46% on the CT/RT arm (p = n.s.). At 4 years the local/regional failure rate was 29% vs. 26% for the RT and CT/RT arms, respectively (p = n.s.). The incidence of first failure in the neck nodes was 10% on the RT arm compared to 5% on the CT/RT arm (p = 0.03 without adjusting for multiple testing) and the overall incidence of distant metastases was 23% on the RT arm compared to 15% on the CT/RT arm (p = 0.03). Treatment related toxicity is discussed in detail, but, in general, the chemotherapy was satisfactorily tolerated and did not affect the ability to deliver the subsequent radiotherapy. Implications for future clinical trials are discussed.

Purpose A two-arm, double-blind, randomized trial was performed to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. Methods and Materials Patients with ductal carcinoma in situ or invasive breast carcinoma who were undergoing external beam radiotherapy to the breast or chest wall were randomly assigned to apply 0.1% MMF or placebo cream daily. The primary study endpoint was the provider-assessed maximal grade of Common Terminology Criteria for Adverse Events, version 3.0, radiation dermatitis. The secondary endpoints included provider-assessed Common Terminology Criteria for Adverse Events Grade 3 or greater radiation dermatitis and adverse event monitoring. The patient-reported outcome measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and a quality-of-life self-assessment. An assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. Results A total of 176 patients were enrolled between September 21, 2007, and December 7, 2007. The provider-assessed primary endpoint showed no difference in the mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs. 1.3 for placebo; p = .18). Common Terminology Criteria for Adverse Events toxicity was greater in the placebo group ( p = .04), primarily from pruritus. For the patient-reported outcome measures, the maximum Skindex-16 score for the MMF group showed less itching ( p = .008), less irritation ( p = .01), less symptom persistence or recurrence ( p = .02), and less annoyance with skin problems ( p = .04). The group's maximal Skin Toxicity Assessment Tool score showed less burning sensation ( p = .02) and less itching ( p = .002). Conclusion Patients receiving daily MMF during radiotherapy might experience reduced acute skin toxicity compared with patients receiving placebo.

The objective of this study was to study the antitumor, host toxicity, and immunomodulatory effects of recombinant interferon-alpha 2b (IFN) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Seventy-one patients with recurrent or metastatic SCCHN were entered into a phase II noncomparative randomized trial of IFN at two dosage schedules. Eligible patients with histologically proven SCCHN were randomized to receive low-dose IFN, 6 x 10(6) U/m2 daily x 3 every 4 weeks or high-dose IFN, 12 x 10(6) U/m2, 3 x/week. Pretreatment levels of natural killer (NK) activity, CD3, CD4, CD5, CD8, CD16, CD19, CD56, DR, and the CD4/CD8 ratio were evaluated for any relationship with survival. The toxicity encountered in patients receiving low-dose IFN was for the most part mild to moderate. With high-dose IFN, toxicity was greater with significantly more episodes of grade 3 and 4 toxicity encountered. Dosage reduction was required in the majority of patients receiving high-dose IFN. Of the four lethal complications, only one was thought to be possibly associated with therapy. Of the 32 evaluable patients receiving low-dose IFN, there were 1 complete response, 1 stable disease, 24 patients with progressive disease, and 6 unevaluable. Of the 29 evaluable patients taking high-dose IFN, there were 2 complete responses, 7 with stable disease, 16 with progressive disease, and 4 patients were unevaluable. Median survival in the two arms was similar (6.2 months). Because it was postulated that a more prolonged exposure to IFN might be needed for it to be effective, patients receivingor = 6 weeks of therapy were evaluated. Median survival in that subset was 10 and 12 months for patients receiving low- and high-dose IFN, respectively. None of the immune parameters tested was a significant predictor of survival when evaluated in all cases entered into study regardless of therapy duration. No difference in baseline NK activity was noted between patients who received6 oror = 6 weeks of IFN (p = 0.90). However, among the 35 patients who receivedor = 6 weeks of therapy, a high baseline NK activity was a significant predictor of the duration of survival (p = 0.04). IFN was well tolerated in patients with recurrent or metastatic SCCHN. The higher incidence of toxicity encountered in the high-dose arm could be ameliorated by reducing the dose 50%. In patients receiving 6 or more weeks of therapy, elevated baseline NK activity was associated with increases in survival, suggesting that IFN may play an immunomodulatory role. Although the overall response rates were low, disease stabilization was noted, suggesting an antiproliferative, noncytotoxic role of IFN in this group of heavily pretreated patients.

From 1981 to 1989, 21 patients with heavily pretreated head and neck cancers were retreated with combined chemotherapy (CT) and irradiation (RT). All patients had previously received radiation therapy with doses of 50-70 Gy. Metastatic disease to lungs and/or osseous sites occurred in 4 patients. Treatment consisted of simultaneous cisplatin, 5-fluorouracil, and external beam radiation therapy, with planned doses of 20 to 70 Gy. The RT+CT was given over 5 consecutive days every 2 weeks. Four patients did not complete treatment due to toxicity (2 patients) or disease progression (2 patients). All patients developed grade 2-3 mucositis. Because of toxicity, 11 patients required treatment delays of 1 to 3 weeks. Clinically complete responses were noted in 10 patients (48%), with partial responses occurring in 5 patients (24%). Of the 21 patients, 18 have died: 13 had local and/or regional recurrence, 2 died of treatment toxicity and 3 died of intercurrent disease. Median time to progression was 5 months (range: 1-15 months). Three patients remain alive with no evidence of disease at 44, 86, and 88 months after retreatment.

The majority of small cell anaplastic tumors of the thyroid gland are generally believed to be non-Hodgkin's lymphomas, including most of those formerly classified as small cell carcinomas. Using a panel of antibodies capable of detecting epithelial, neuroendocrine, and B and T cells in paraffin-embedded tissue sections, we studied 68 thyroid neoplasms in which the original diagnosis was small cell carcinoma or lymphoma. Sixty-three of the tumors were identified as lymphomas of B-cell origin on the basis of L26 reactivity used in conjunction with light chain restriction and MB2 immunostaining. Two additional tumors were classified as lymphomas of indeterminate phenotype. Immunophenotyping indicated an epithelial origin in the remaining three tumors. No cases of medullary carcinoma were detected by immunostaining. Histologic review revealed a predominance of large cell and immunoblstic lymphomas, with low-grade lymphomas of mucosa-associated lymphoid tissue histology accounting for only five cases. Our findings indicate that the majority of small cell anaplastic tumors of the thyroid are B-cell lymphomas. Although primary small cell carcinoma of the thyroid may rarely occur, this diagnosis should not be made without immunohistologic confirmation.

From 1953 to 1975, 330 children received megavoltage for benign or malignant tumors. Fourteen subsequently developed second neoplasms. The 30-year cumulative incidence of second neoplasms was 9.6%. The incidence of second malignant neoplasms may be lower following megavoltage radiation than following orthovoltage radiation.

Seventeen patients with pineal tumors and one ectopic (suprasellar) germinoma were treated with radiation therapy. Surgery was restricted to decompression in 16 patients, and only two patients had resection of the tumor. Thirteen of 18 patients are alive without evidence for disease with a ten-year survival rate of 88%. The tumor dose ranged from 4000 rads to 6000 rads. No age or dose dependence in survival was noted, but patients with whole brain irradiation or generous volume to include ventricular system had better survival. No case of spinal metastasis was noted. The possibility of increased incidence of meningeal seeding following surgical intervention is considered. From their data, the authors feel that radiation therapy with or without surgical decompression should be the primary treatment for pinealoma. Surgery can be used for diagnosis and/or treatment of patients who show delayed response to radiation. Recommendation is made for the use of whole brain irradiation to 4000 rads followed by a boost to the tumor area to 5000 rads.

Previous reports of radiation-related neoplasia have relied primarily upon patients treated by orthovoltage to low doses for benign disease. This survey is believed to be the first to assess the incidence of second neoplasms following megavoltage therapy. The source was the records of all long-term pediatric survivors (88 patients) who were treated with megavoltage radiation (cobalt 60) at the University of Minnesota. There was an average follow-up period of 14 years during which 7 second neoplasms were discovered (8%). Five were not associated with prior radiation. Both radiation-related neoplasms were associated with low doses and one was without significant morbidity. Two of the seven neoplasms were malignant; one was not associated with radiation while the other was associated with prolonged chemotherapy and low dose radiation (1%). The only fatal second neoplasm was not associated with radiation but developed 5 years after prolonged chlorambucil treatment. This review reveals the tendency of childhood cancer victims to develop other neoplasms regardless of radiation. The finding of neoplasia induction only at low radiation doses supports the Gray hypothesis of decreased tumor induction at high doses through increased cell killing.

Ninety-six patients with cancer of the tonsillar region in all stages were studied to compare full-course radiation therapy with surgical salvage to planned radiation and surgery. Full-course radiation therapy was effective in controlling T1 and T2 tumors without neck node involvement. Combined therapy was much more effective in treating T3 tumors with neck node disease. Patients with T4 tumors did poorly regardless of therapy.

High energy photon beams traversing large iatrogenic air cavities can lead to surface underdosage and overdosage because of high exit dose. A water bag bolus in such external cavities is a remarkably simple and reproducible means of producing dosage homogeneity.