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Background/objectives Childhood cranial radiation has irreversible neurocognitive effects. Hyperfractionated radiation therapy (HFX) for acute lymphoblastic leukemia (ALL) was randomized against conventionally fractionated radiation therapy (CFX) in the DFCI 87-01/91-01 trials attempting to minimize these effects. When neurocognitive testing 8-year posttreatment demonstrated no difference, this strategy was abandoned. The objective of this study was to evaluate late social outcomes among patients who received HFX compared to CFX as part of the DFCI 87-01/91-01 trials. Methods This retrospective chart review examined all patients treated according to the DFCI 87-01/91-01 trials at the McMaster Children's Hospital in Hamilton, Canada. Patients

ContextThe 15-item University of Washington Quality of Life questionnaire-Radiation Therapy Oncology Group (RTOG) modification (UW-QOL-RTOG modification) has been used in several trials of head and neck cancer conducted by NRG Oncology such as RTOG 9709, RTOG 9901, RTOG 0244, and RTOG0537.ObjectivesThis study is an exploratory factor analysis (EFA) to establish validity and reliability of the instrument subscales.MethodsEFA on the UW-QOL-RTOG modification was conducted using baseline data from NRG Oncology's RTOG 0537, a trial of acupuncture-like transcutaneous electrical nerve stimulation in treating radiation-induced xerostomia. Cronbach α coefficient was calculated to measure reliability; correlation with the University of Michigan Xerostomia Related Quality of Life Scale was used to evaluate concurrent validity; and correlations between consecutive time points were used to assess test-retest reliability.ResultsThe 15-item EFA of the modified tool resulted in 11 items split into four factors: mucus, eating, pain, and activities. Cronbach α ranged from 0.71 to 0.93 for the factors and total score, consisting of all 11 items. There were strong correlations (ρ≥0.60) between consecutive time points and between total score and the Xerostomia Related Quality of Life Scale total score (ρ>0.65).ConclusionThe UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The modified tool has acceptable reliability, concurrent validity, and test-retest reliability in this patient population, as well as the advantage of having being shortened from 15 to 11 items.

Childhood cranial radiation has irreversible neurocognitive effects. Hyperfractionated radiation therapy (HFX) for acute lymphoblastic leukemia (ALL) was randomized against conventionally fractionated radiation therapy (CFX) in the DFCI 87-01/91-01 trials attempting to minimize these effects. When neurocognitive testing 8-year posttreatment demonstrated no difference, this strategy was abandoned. The objective of this study was to evaluate late social outcomes among patients who received HFX compared to CFX as part of the DFCI 87-01/91-01 trials.This retrospective chart review examined all patients treated according to the DFCI 87-01/91-01 trials at the McMaster Children's Hospital in Hamilton, Canada. Patients18 years at diagnosis and who have attended follow-up clinic since January 1, 2000 were included in this study. Social outcomes and IQ test results were examined for trends. Demographics and outcomes were presented with descriptive statistics.We identified 57 DFCI 87-01/91-01 trial participants: 14 received HFX, 29 received CFX, and 14 received no radiation. There were no demographic differences between the groups. HFX survivors were more likely to be living independently (64% vs. 28%, P = 0.02) and engaged in long-term relationships (57% vs. 25%, P = 0.04) than CFX. Nonsignificant trends suggested that HFX survivors may be more financially independent, employed full-time, had fewer educational difficulties in school, and higher scores on neuropsychological testing. Data trends, although not significant, persisted in logistic regression analysis when accounting for age.Long-term social outcomes were better among ALL survivors who received HFX than CFX. A wider study involving all patients enrolled on DFCI 87-01/91-01 protocols should be conducted to reconsider radiation protocols for ALL.

We compared the management and outcome of glottic cancer in Ontario, Canada to that in the Surveillance, Epidemiology and End Results (SEER) Program areas in the United States to determine whether the greater use of primary radiotherapy with surgery reserved for salvage in Ontario was associated with similar survival and better larynx retention rates than the U.S. approach where primary surgery is used more often. Electronic, clinical and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Initial treatment and survival in patients diagnosed in the SEER areas from 1988 through 1994 were compared to patients from Ontario diagnosed from 1982 through 1995. Actuarial laryngectomy rates were compared for patients over 65 at diagnosis in the two regions. Analyses were conducted over all cases and stratified by disease stage. In localized disease (T1 or T2), conservative treatment was the most common initial treatment in both regions, although total laryngectomy was used more often in SEER than Ontario (6.2% vs. 0.2%, respectively, P P ⩽ .001). Over all cases, the relative survival rate was 80% in Ontario at 5 years compared to 78% in SEER ( P = .33). In localized disease, the relative survival rates were 4 to 5% higher in Ontario from the second year on, while in advanced disease 2 to 3% higher rates in SEER did not approach statistical significance. Actuarial laryngectomy rates at 3 years differed between the two regions, with a 4% higher rate in SEER ( P = .01). In localized disease, 12.6% of Ontario patients had a laryngectomy by 3 years postdiagnosis compared to 17.9% in SEER ( P = .05). In advanced disease, the rates were 63.3% and 79.2%, respectively ( P = .07). There are large differences in the management of glottic cancer between the SEER areas of the U.S. and Ontario and no evidence that a policy emphasizing radiotherapy with surgery reserved for salvage is associated with worse survival. Ultimate laryngectomy rates are lower in Ontario for localized disease and may be lower for advanced disease. Conservation treatment should be used for localized disease while the treatment decision in advanced disease may be especially sensitive to patient values for voice retention versus initial cure.

Background A systematic review was conducted to develop clinical recommendations for concomitant chemotherapy (CT) and radiotherapy (RT) in patients with locally advanced squamous cell head and neck cancer (SCHNC). Methods Results of published randomized controlled trials (RCTs) were pooled using Meta-analyst0.988 software. Results A pooled analysis of 18 RCTs (20 comparisons) involving 3,192 patients detected a reduction in mortality for concomitant therapy compared with RT alone (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.52–0.74; relative risk, 0.83; risk reduction, 11%; p < .00001). Platinum-based regimens involving 1,514 patients from nine trials (10 comparisons) were most effective (OR, 0.57; 95% CI, 0.46–0.71; p < .00001; risk reduction, 12%). Concomitant therapy produced more acute adverse effects than RT alone. Conclusion Platinum-based concomitant CT and RT is superior to conventional RT alone in improving survival in locally advanced SCHNC. Subgroup analyses can be used to help in choosing the most appropriate concomitant regimen. © 2001 John Wiley & Sons, Inc. Head Neck 23: 579–589, 2001.

BACKGROUND The objectives of this study were 1) to describe patterns of use of computed tomography (CT) in laryngeal carcinoma, and 2) to characterize the contribution of CT to the T classification of laryngeal carcinoma. METHODS The study population comprised 1195 patients with laryngeal carcinoma diagnosed from 1982 through 1995 chosen randomly from the Ontario provincial cancer registry. A chart review was conducted to obtain data on each case. Patient-related, tumor-related, and health-system-related factors were analyzed to identify factors associated with the use of CT. Descriptions of clinical exams and CT reports were reviewed to see how CT information modified T classification. Actuarial local control and cause specific survival curves were plotted by clinical T classification without and with CT to evaluate stage migration. The percentage of the variance in outcome explained by T classification in a Cox analysis was used to evaluate whether the prognostic accuracy of T classification was improved with the use of information from CT. RESULTS Patients with glottic (20.1%) and supraglottic (41.7%) carcinoma underwent CT. The use of CT increased over time in glottic and supraglottic carcinoma combined from 17.2% in 1982–5 to 33.9% in 1991–5. Computed tomography was used less often in older patients with a 16% (95% confidence interval, 5– 27%) decrease in the odds of having CT with each 10-year age increment. Computed tomography use varied considerably across the cancer center regions in Ontario. Computed tomography altered the T classification in 20.2% of those patients who had CT, with most being “upstages.” Stage migration due to CT was demonstrated. Using information from CT in the assignment of T classification for 27.8% of this study population did not make a significant contribution to the ability of T classification to predict outcome over the entire group. CONCLUSIONS There is large variation in the use of CT among different age groups and regions. The ability to compare outcomes by stage across geographic areas is compromised when the use of CT varies. Cancer 2001;91:394–407. © 2001 American Cancer Society.

The 1987 TNM classification system modified T and N definitions for squamous cell carcinomas of the head and neck. It did not change stage groupings (I through IV). The primary purpose of clinical staging is to divide patients into prognostically meaningful groups. The 1987 changes to the TNM T and N descriptions may not have removed the previously established heterogeneity within stage groups III and IV which existed before 1987. The development of a stage grouping system called TANIS (the T And N Integer Score), which is formed by adding the integer values of the T and N classifications, is reported herein. We compared the prognostic performance of T, N, TNM stage group, and TANIS stage for radiotherapy response and survival using data from 86 patients with newly diagnosed, measurable TNM II (oral cavity), and localized TNM III-IV squamous cell carcinomas of the head and neck, excluding nasopharynx, who were randomized to test 5-fluorouracil-methotrexate sequencing. The sequencing of chemotherapy was shown to make no difference to prognosis. All patients received 60 Gy of radiotherapy in 6 weeks. As compared to T, N, and the TNM stage group system, TANIS was the single best predictor for a complete response to radiotherapy (p = 0.0005). TANIS was also the single best predictor for survival from randomization (p = 5 × 10−6). With the 86 patients divided into three groups (TANIS 2 to 3, 4, and 5 to 7), TANIS provided a better prognostic discrimination than did the TNM stage grouping method (TNM II, III, and IV). TANIS is a single index that combines T and N information in a simple way which was more strongly associated with radiotherapy response and survival than the traditional TNM stage groups.

Radiation therapy is an important curative modality in the treatment of patients with head and neck cancer. However, radiation-induced changes in the oral cavity, such as xerostomia and mucositis, are among the most debilitating treatment sequelae experienced by patients undergoing radiation therapy, and attempts at ameliorating these side effects have been poor at best. Pilocarpine has been approved for post-radiation xerostomia, and the effect of its use during radiation therapy on salivary flow, xerostomia, mucositis, and quality of life (QOL) was assessed in a phase III study conducted by the Radiation Therapy Oncology Group (RTOG 97-09). In total, 245 evaluable patients were randomized to pilocarpine or placebo. Selected patients were required to haveor = 50% of the volume of the major salivary glands receiveor = 50Gy; to agree to provide stimulated and unstimulated samples of saliva (measured in g) before treatment, at the end of treatment, and 3 and 6 months after completion of radiation therapy; and to complete the University of Washington Head and Neck Symptom Scale. Following the completion of radiation therapy, the average unstimulated salivary flow was statistically greater in the pilocarpine group, whereas no difference was noted following parotid stimulation. There was no effect on the amelioration of mucositis. The results of the QOL scales did not reveal any significant difference between the pilocarpine and placebo groups with regard to xerostomia and mucositis. The significant difference in unstimulated salivary flow supports the concomitant use of oral pilocarpine to decrease radiation-associated xerostomia. However, the absent correlation between improved salivary flow and QOL scores is of some concern (though not a new finding) and may be related to the existence of comorbidities and the lack of effect on mucositis.

Purpose: This population-based study describes the treatment of early glottic cancer in Ontario, Canada and assesses whether treatment variations were associated with treatment effectiveness. Methods and Materials: We studied 491 T1N0 and 213 T2N0 patients. Data abstracted from charts included age, sex, stage, treatment details, disease control, and survival. Results: The total dose ranged from 50 to 70 Gy, and the daily dose ranged from 1.9 to 2.8 Gy. In 90%, treatment duration was between 25 and 50 days. Field sizes, field reductions, beam arrangement, and beam energy varied. Late treatment breaks occurred in 13.6% of T1N0 and 27.1% of T2N0 cases. Local control was comparable to other reports for T1N0 (82% at 5 years), but was only 63.2% in T2N0. Variables associated with local failure in T1N0 were age less than 49 years (relative risk [RR], 3.21; 95% confidence interval [CI], 1.49‐6.90) and >3 treatment interruption days (RR, 2.43; 95% CI, 1.00‐5.91). In T2N0, these were field reduction (RR, 2.33; 95% CI, 1.23‐4.42) and late treatment breaks (RR, 2.19; 95% CI, 1.09‐4.41). Conclusion: Some aspects of treatment for early glottic cancer were associated with worse local control. Problems with protracted treatment are of particular concern, underscoring the need for randomized studies to intensify radiotherapy. © 2006 Elsevier Inc. Laryngeal cancer, Practice variations, Survival, Local control, Population-based.

Purpose: We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States. Methods: Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265). We also compared laryngectomy rates at 3 years in those patients 65 years and older at diagnosis. Results: Radical surgery was more commonly used in SEER, with absolute differences increasing with increasing stage: I/II, 17%; III, 36%; and IV, 45%. The 5-year survival rates were 74% in Ontario and 56% in SEER for stage I/II disease (P = .01), 55.7% in Ontario and 46.8% in SEER for stage III disease (P = .40), and 28.5% in Ontario and 29.1% in SEER for stage IV disease (P = .28). Cancer-specific survival results mirrored the overall survival results with the exception of stage IV disease, for which 34.6% of Ontario patients survived their cancer compared with 38.1% in SEER (P = .10). This stage IV difference was more pronounced when we further controlled for possible cause of death errors by restricting the comparison to patients with a single primary cancer (P = .01). Three-year actuarial laryngectomy rates differed. In stage I/II, these rates were 3% in Ontario compared with 35% in SEER (P < 10−3). In stage III disease, the rates were 30% and 54%, respectively (P = .03), and in stage IV disease they were 33% and 64% (P = .002). Conclusion: There are large differences in the management of supraglottic cancer between the SEER areas of the United States and Ontario. Long-term larynx retention was higher in Ontario, where radiotherapy is widely regarded as the treatment of choice and surgery is reserved for salvage. In stages I to III, survival was similar in the two regions despite the differences in treatment policy. In stage IV, there may be a small survival advantage in the U.S. SEER areas related to the higher use of primary surgery.

Purpose: The probability of treatment resistant cells developing in a tumor, such as small cell lung cancer (SCLC) which has a rapid cell cycle time, is a function of the number of tumor cells present and of time. Theoretically, the development of resistance to chemotherapy and radiotherapy should be minimized by using all treatment modalities early in the treatment program. Methods and Materials: The importance of the timing of loco-regional radiotherapy was assessed in a multi-institution randomized study. Three hundred and eight patients with limited small cell lung cancer (LSCLC) were given three cycles of cyclophosphamide, doxorubicin and vincristine alternating with three cycles of etoposide and cisplatin. In addlition, patients were randomized to receive locoregional radiotherapy: 40 Gy in 15 fractions in 3 weeks with treatment planning techniques to limit the spinal cord dose to be ≤ 35 Gy either with the first cycle (early) or with the sixth cycle of chemotherapy (late). Responding patients received prophylactic brain irradiation (25 Gy in 10 fractions in 2 weeks) after completion of locoregional radiotherapy and chemotherapy. Results: 96% of the 155 eligible patients allocated to the "early" arm and 87% of the 153 allocated to the "late" arm received locoregional radiotherapy; 26 patients did not receive locoregional radiotherapy. The mean field sizes were similar in both arms. The mean radiation doses were significantly less in the "early" arm ( p = 0.0319 Wilcoxon rank sum test). Any differences in the frequency of toxicities were minor. All patients have been followed for at least 2 years and the median follow up is 4 years. 64% had a complete response in the "early" arm compared with 56% in the "late" arm ( p = 0.137). Survival was measured from the start of chemotherapy. There was a significant improvement in survival in the "early" arm; median survival was 21.2 months compared with 16.0 months in the "late" arm ( p = .008 log rank test). Survival at 2, 3, and 4 years was 40%, 32%, and 25%, respectively, for the "early" arm and 33%, 22%, and 15% for the "late" arm. There were 232 (75%) recurrences among those patients whose disease recurred. The proportion who had local recurrence within the radiation field was 41% and 39% for "early" and "late" treatment arms respectively. The proportion of brain metastases in the "late" arm (28%) was significantly higher than in the "early" arm (18%) p = .0425 Fishers' exact test. Conclusion: We conclude that early administration of locoregional radiotherapy in a combined modality treatment is superior to late consolidative locoregional radiotherapy in limited small cell lung cancer.

Forty-two patients, with a variety of advanced pelvic malignancies, have been treated with a hypofractionated radiotherapy regimen. The most common schedule was 30 Gy in three fractions at monthly intervals. This has provided effective palliation with acceptable morbidity in the select patient group treated. The results in advanced rectal and ovarian tumors were particularly encouraging. The most effective dose/fraction and interfraction interval is, at present, under active investigation within our institution.

Twenty-four patients with Chordoma who received our or more courses of megavoltage radiation therapy following biopsy or incomplete resection were reviewed. The uncorrected survival rate at five years was 62 %, and at 10 years was 28 %, but most patients had clinically detectable residual Chordoma present at the time of death or last follow-up. The duration of symptomatic improvement following irradiation ranged from a few months to 18 years, median 3.5 years. Detailed dose-time and symptomatic response data for 56 patients from this series and from the literature who were treated by conventional daily fractionated megavoltage irradiation show no convincing evidence that symptomatic relief is more likely after high doses than after total doses of only 4000 to 5500 cGy. Patients are rarely cured of chordoma by partial tumor resection and conventional radiation. Four patients received multiple fractions of 100 cGy each day either as retreatment for recurrence, or as initial treatment. Symptomatic responses, and decreases in the size of tumor masses, were swan following total doses ranging from 2000 cGy/20 fractions/5 days/4 × 3 hourly fractions each day to 4000 cGy/40 fractions/12 days/4 × 3 hourly fractions each day. The short duration of follow-up in these patients prevents comparison with conventional fractionation. However, this technique presents one possible new approach for the treatment of Chordoma.