A Practical Radiotherapy Treatment Planning Technique for Second-Incidence Cancers That Incorporates Complete Organ-At-Risk Dose History.

INTRODUCTION: Patients requiring treatment for second cancer incidences present unique radiotherapy plan development challenges. Historical dose delivered to organs at risk must be accounted for to properly estimate lifetime toxicity risks, but historical dose delivered to the region now occupied by tumours does not contribute to the prescription dose. Treatment planning systems permit inclusion of a base plan but do not provide the ability to manipulate it. We present a technique, dose cropping, which incorporates organ-at-risk dose history into the base plan while selectively excising dose history to diseased tissues now occupied by tumours. A retrospective plan comparison is performed to assess the effectiveness of dose cropping. METHODS AND MATERIALS: Nine patients who received a second course of radiotherapy for cancers of the head-and-neck were replanned using the proposed technique. Clinical second courses and replans were compared on the basis of conformity index, heterogeneity index, maximum point dose, tissue control probability (TCP), normal tissue complication probability (NTCP), and whether the planning guidelines could be met by the treatment planning system. Replan constraints and guidelines followed the clinical treatment. In addition, a tissue recovery model was incorporated, applied to both clinical and replan courses, and compared to estimate the relevance of the dose cropping technique in such regimes. RESULTS AND DISCUSSION: Replans had reduced organ-at-risk maximum point doses (5 Gy for spinal cord, 4 Gy for brainstem), NTCP (2.9% median reduction), and were able to more consistently achieve the V95% > 98% coverage target regardless of the tissue recovery model. At the same time, replans using the dose cropping technique were statistically indistinguishable from clinical second courses on the basis of plan conformity, heterogeneity, or TCP (P > .31 in all cases). CONCLUSIONS: Dosimetric history cropping is a valuable and widely applicable technique for second cancer radiotherapy planning. It also provides a natural means to incorporate tissue recovery models, biologically effective dose conversion, and NTCP and TCP model evaluation.

Quality of life and swallowing with standard chemoradiotherapy versus accelerated radiotherapy and panitumumab in locoregionally advanced carcinoma of the head and neck: A phase III randomised trial from the Canadian Cancer Trials Group (HN.6).

AIM: To compare quality of life (QOL) between standard (SFX) chemoradiotherapy (arm A) and altered fractionation radiotherapy (AFX) with panitumumab (PMab; arm B). METHODS: Patients with T any N + M0 or T3-4N0M0 squamous cell head-neck carcinoma were randomised to SFX (70 Gy/35/7 wks) plus cisplatin (100 mg/m2 IV × 3) versus AFX (70 Gy/35/6 wks) plus PMab (9 mg/kg IV × 3). QOL was collected at baseline, end of radiation therapy (RT) and 2, 4, 6, 12, 24 and 36 months post-RT using the Functional Assessment of Cancer Therapy Head and Neck (FACT-H&N), MD Anderson Dysphagia Index (MDADI) and SWAL-QOL. We hypothesised a 6-point more favourable change in FACT-H&N score from baseline to 1 year in arm B over arm A. RESULTS: Among 320 patients, median follow-up was 46 (range: 0.1-64.3) months, median age 56, 84% male, Eastern Cooperative Oncology Group PS 0 (71%), 1 (29%). Primary site was oropharynx in 81% (p16+ 68%, p16- 16%, missing 16%). Baseline scores did not differ by arm (A/B): FACT-H&N 116.5/115, MDADI Global 83/77, SWAL-QOL General 67/68. At 1 year, no difference was seen between arms in FACT-H&N change from baseline: A -1.70, B -4.81, p = 0.194. Subscale change scores by arm were (A/B): last week RT, FACT-Physical (-11.6, -10, p = 0.049), MDADI Physical (-40.4, -33.9, p = 0.045), and SWAL-QOL Eating Duration (-61.2, -51.2, p = 0.02), Eating Desire (-53.3, -43.9, p = 0.031) and Mental Health (-42, -32.6, p = 0.009); 4 months, HN subscale (-7.7, -10, p = 0.014). No clinically important differences by arm were seen post-treatment. CONCLUSIONS: PMab with AFX did not durably improve QOL or swallowing as compared with SFX with cisplatin. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00820248.

Comparison of toxicity associated with early morning versus late afternoon radiotherapy in patients with head-and-neck cancer: a prospective randomized trial of the National Cancer Institute of Canada Clinical Trials Group (HN3).

PURPOSE: Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G(1) phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT. METHODS AND MATERIALS: A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system. RESULTS: Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025). CONCLUSION: In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving >/=66 Gy and in patients who smoked during therapy.

Effect of margins on ipsilateral breast tumor recurrence after breast conservation therapy for lymph node-negative breast carcinoma.

BACKGROUND: Breast conservative surgery (CS) with radiotherapy (RT) is the most commonly used treatment for early-stage breast carcinoma. However, there is controversy regarding the importance of the pathologic margin status on the risk of ipsilateral breast tumor recurrence (IBTR). The current study evaluated the effect of the pathologic margin status on IBTR rates in a cohort of women with lymph node-negative breast carcinoma treated with CS and RT. METHODS: Between August 1980 and December 1994, 452 women with pathologically lymph node-negative breast carcinoma were treated with CS and RT at Westmead Hospital (Westmead, Australia). Central pathology review was performed for all women. The final margins were negative for 352 women (77.9%), positive (invasive and/or in situ) for 42 women (9.3%), and indeterminate for 58 women (12.8%). Information regarding an extensive intraductal component (EIC), lymphovascular invasion, pathologic tumor size, histologic grade, and nuclear grade was available for most women. After macroscopic total excision of the tumor, all women received whole-breast irradiation (usually 45-50.4 grays [Gy]) and the majority of women also received a local tumor bed boost (range, 8-30 Gy). RESULTS: After a median follow-up of 80 months, 34 women (7.5%) developed an IBTR. The crude 5-year rates of IBTR for women with negative margins, positive margins, and indeterminate margins were 3.1%, 11.9%, and 6.9%, respectively. For women with negative margins, the 5-year and 10-year actuarial rates of freedom from IBTR were 96% and 92%, respectively, compared with 88% and 75%, respectively, for women with positive margins (P = 0.003). Univariate analysis demonstrated that the only factors associated with a significantly higher risk of IBTR were age at diagnosis (P < 0.050) and margin status (P = 0.005). Multivariate analysis showed that both age and margin status were independent predictors of IBTR. None of 24 patients with an EIC and negative margins were found to have developed an IBTR. CONCLUSIONS: The results of the current study were comparable to other published reports and supported the association of higher IBTR rates with positive or indeterminate margins compared with negative, pathologic margins. Furthermore, young age (age < 35 years at diagnosis) was associated with the highest risk of IBTR regardless of margin status.

Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15).

PURPOSE: This multi-institutional Phase III randomized study compared 10 Gy single-fraction radiotherapy (RT) with 20 Gy in five fractions in the palliation of thoracic symptoms from lung cancer. METHODS AND MATERIALS: The primary end point was palliation of thoracic symptoms at 1 month after RT, evaluated by a patient-completed daily diary card. Secondary end points included quality of life, toxicity, and survival. RESULTS: Most (69%) of 230 patients randomized had locally advanced disease unsuitable for curative treatment. The treatment arms were well balanced with respect to the known prognostic factors. At 1 month after RT, no difference was found in symptom control between the two arms, as judged by the daily diary scores. The changes in the scores on the Lung Cancer Symptom Scale indicated that the fractionated RT (five fractions) group had greater improvement in symptoms related to lung cancer (p = 0.009), pain (p = 0.0008), ability to carry out normal activities (p = 0.037), and better global quality of life (p = 0.039). The European Organization for Research and Treatment of Cancer QLQ-C30 scores showed that patients receiving five fractions had a greater improvement in scores with respect to pain (p = 0.04). No significant difference was found in treatment-related toxicity. Patients who received five fractions survived on average 2 months longer (p = 0.0305) than patients who received one fraction. CONCLUSION: Although the two treatment strategies provided a similar degree of palliation of thoracic symptoms, the difference in survival between the two study arms was of a clinically relevant magnitude.