Elapsed treatment days--a critical item for radiotherapy quality control review in head and neck trials: RTOG report.

For all randomized trials since 1978, the Radiation Therapy Oncology Group has required the study chairman for radiation therapy to review the treatment given to each patient. The chairman scores the compliance of the treatment borders, total dose, fraction, and total elapsed time relative to the protocol prescription at the primary site, regional nodes, and any critical structure. The individual parameters are then considered together to derive an "overall" treatment score. For two RTOG head and neck studies in patients with moderately and very advanced carcinomas, the "overall" treatment was classified as unacceptable if the treatment at primary was scored unacceptable with respect to dose, fractionation, and field borders. However, prolonged elapsed treatment was not included. Analysis of these studies with 426 evaluable patients was performed to assess the relationship of unacceptable "overall" treatment compliance with outcome. Patients with prolonged treatment elapsed days (14 days beyond the protocol prescription) exhibited significantly poorer loco-regional control (13% vs. 27% at 3 years with p = .007) and absolute survival (13% vs. 26% at 3 years with p = .01). As a result, the criteria for unacceptable "overall" treatment were revised to include prolonged elapsed treatment days. Further multivariate analyses showed the revised criteria identified patients with significantly poorer loco-regional control and absolute survival even after adjusting for other prognostic factors.

The role of hemoglobin concentration in the outcome of misonidazole-sensitized radiotherapy of head and neck cancers: based on RTOG trial #79-15.

Recent data from the DAHANCA (Danish Head and Neck Cancer) 2 study implies a positive effect of high hemoglobin concentration in concert with misonidazole for the treatment of head and neck cancers by radiotherapy. We have therefore reviewed and updated our analysis of RTOG protocol 79-15, which included the effect of misonidazole plus radiotherapy in a presumably similar population. Despite additional follow-up and more sophisticated analysis, our analysis does not demonstrate an influence of hemoglobin concentration on any of the outcome measures we examined. Possible explanations for the difference in findings of RTOG 79-15 and DAHANCA 2 are discussed. Radiation therapy of head and neck squamous cancers, Hypoxia and hemoglobin conc. in head and neck cancers, Oral cavity cancer, Effect of radiation therapy, Oropharynx cancer, Hemoglobin and radiotherapy, Hemoglobin concentration, Effect upon radiotherapy, Irradiation of oropharynx cancer, Hgb effect.

Tumor regression and other prognosticators in advanced head and neck cancers: a sequel to the RTOG methotrexate study.

The randomized Radiation Therapy Oncology Group (RTOG) Methotrexate trial in advanced squamous cancers of the head and neck has reported no control or survival benefits when the chemotherapy adjuvant was administered to patients just prior to definitive irradiation. The required data collection and outcome reporting among 146 patients bearing oral cavity primaries and 354 patients with oropharyngeal cancers has allowed a multi-variate approach seeking answers to many unresolved questions. As anticipated, the ability to control these squamous cancers is largely a function of size (T & N stage) with a superior clearance among T3-4 primaries of the oropharynx (66%) contrasted to identically staged oral cavity tumors (48%). Adjusted median survival is more than doubled to 26.6 months or 19.8 months among oral cavity and oropharynx patients respectively, when compared to the 8 month median survival when neither primary nor cervical nodes are controlled. Lymph node deposits also impact upon survival, especially among oropharynx patients where the 17.6 month adjusted median survival among N0 patients declines to 11.0 months when the primaries are associated with N3 nodes. Surprisingly, the ability to control nodel deposits of all sizes (N1, N2, or N3) is superior among oropharynx patients when compared with identical oral cavity metastases (e.g. 71.4% adjusted clearance in N3 oropharyngeal deposits versus 46.1% in N3 nodes secondary to oral cavity primaries). Adjustments for maldistribution of advanced N-stages in association with T-4 primary stage eliminated an apparent T-stage effect upon nodal clearance within both anatomic regions. Finally, the association of T and N-stage upon distant metastases was investigated, with the surprising conclusion that neither initial T nor N-stage exerts any apparent influence on the observed 10-12% occurrence. The interrelationship of these various prognostic variables is explored using the Cox and logistic models.

Postirradiation sarcoma of the head and neck: a report of three late sarcomas following therapeutic irradiation for primary malignancies of the paranasal sinus, nasal cavity, and larynx.

Sarcoma of the head and neck region following irradiation for primary malignancy other than retinoblastoma has rarely been reported. Three cases of postirradiation sarcoma arising in the head and neck region following definitive radiotherapy for primary malignancies of the nasal cavity, paranasal sinuses, and larynx are presented. The intervals from initial radiation to diagnosis of sarcoma were 10 years, 10 1/2 years, and 12 1/2 years, respectively. The dosage ranged from 6000--6400 rads using conventional fractionation (1750--1811 ret) on a 60Cobalt teletherapy unit. Methotrexate (25 mg I. V. every three days for seven doses) was utilized during the initial course of radiation in two of the three patients. The cases conform well to established criteria for the diagnosis of radiation-induced sarcoma. Postirradiation sarcoma of the head and neck region is a remote hazard that must be weighed against the benefits of curative radiation therapy, particularly when treating in the presence of bone disease or when treating retinoblastoma or benign lesions.

Irradiation of stage I and II Hodgkin's disease.

One must conclude on the basis of the above analysis that tumor doses in excess of 3,600 or 4,000 rads add only to morbidity, and not to local control. Secondly, the technique of irradiating involved lymph node groups only, leaving other areas to be treated "later," apparently denies the possibility of cure to a significant number of patients with early stage Hodgkin's disease. Recurrence or extension almost uniformly leads to eventual death from disease despite retreatment. No case of second primary cancer has been documented in the patient population included in this report. However, the number at risk is relatively small and chemotherapy was reserved only for generalized recurrence. Since the reported 20 times expected incidence occurred with the combination of total-nodal and multple-agent chemotherapy, one would not expect an increased incidence of second primary lesions in this series.