Induction chemotherapy followed by alternating chemo-radiotherapy in stage IV undifferentiated nasopharyngeal carcinoma

In locally advanced undifferentiated nasopharyngeal carcinoma (UNPC), concomitant chemo-radiotherapy is the only strategy that gave better results over radiation alone in a phase III trial. Adding effective chemotherapy to a concomitant chemo-radiotherapy programme may be a way to improve the results further. 30 patients with previously untreated T4 and/or N2–3 undifferentiated nasopharyngeal carcinoma were consecutively enrolled and initially treated with 3 courses of epidoxorubicin, 90 mg/m2, day 1 and cisplatin, 40 mg/m2, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/m2/day, days 1–4 and fluorouracil, 200 mg/m2/day, days 1–4, i.v. bolus, (weeks 1, 4, 7) alternated to 3 courses of radiation (week 2–3, 5–6, 8–9–10), with a single daily fractionation, up to 70 Gy. WHO histology was type 2 in 30% and type 3 in 70% of the patients. 57% had T4 and 77% N2–3 disease. All the patients are evaluable for toxicity and response. All but one received 3 courses of induction chemotherapy. Toxicity was mild to moderate in any case. At the end of the induction phase 10% of CRs, 83.3% of PRs and 6.7% of SD were recorded. All the patients but one had the planned number of chemotherapy courses in the alternating phase and all received the planned radiation dose. One patient out of 3 developed grade III–IV mucositis. Haematological toxicity was generally mild to moderate. At the final response evaluation 86.7% of CRs and 13.3% of PRs were observed. At a median follow-up of 31 months, 13.3% of patients had a loco-regional progression and 20% developed distant metastases. The 3-year actuarial progression-free survival and overall survival rates were 64% and 83%. Induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients' compliance optimal. This approach showed a very promising activity on locally advanced UNPC and merits to be investigated in phase III studies. © 2000 Cancer Research Campaign http://www.bjcancer.co

Ipsilateral irradiation for well lateralized carcinomas of the oral cavity and oropharynx: results on tumor control and xerostomia

<p>Abstract</p> <p>Background</p> <p>In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing. The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy.</p> <p>Methods</p> <p>Twenty consecutive patients with lateralized carcinomas of the oral cavity and oropharynx were treated with a prospective management approach using ipsilateral irradiation between 2000 and 2007. This included 8 radical oropharyngeal and 12 postoperative oral cavity carcinomas, with Stage T1-T2, N0-N2b disease. The actuarial freedom from contralateral nodal recurrence was determined. Late xerostomia was evaluated using the European Organization for Research and Treatment of Cancer QLQ-H&N35 questionnaire and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.</p> <p>Results</p> <p>At a median follow-up of 58 months, five-year overall survival and loco-regional control rates were 82.5% and 100%, respectively. No local or contralateral nodal recurrences were observed. Mean dose to the contralateral parotid gland was 4.72 Gy and to the contralateral submandibular gland was 15.30 Gy. Mean score for dry mouth was 28.1 on the 0-100 QLQ-H&N35 scale. According to CTCAE v3 scale, 87.5% of patients had grade 0-1 and 12.5% grade 2 subjective xerostomia. The unstimulated salivary flow was > 0.2 ml/min in 81.2% of patients and 0.1-0.2 ml/min in 19%. None of the patients showed grade 3 xerostomia.</p> <p>Conclusion</p> <p>In selected patients with early and moderate stages, well lateralized oral and oropharyngeal carcinomas, ipsilateral irradiation treatment of the primary site and ipsilateral neck spares salivary gland function without compromising loco-regional control.</p

Prospective evaluation of weekly concomitant tumor bed boost with three-week hypofractionated whole breast irradiation in early breast cancer

Objectives: A prospective study was conducted to assess the acute and late toxicity of hypofractionated whole breast irradiation with a weekly concomitant boost for women with early breast cancer (EBC). Methods: Women with EBC who underwent breast-conserving surgery were eligible. A dose of 40Gy in 15 fractions over 3 weeks was delivered to the whole breast with a concomitant weekly boost to the post-operative cavity of 3Gy in three fractions. Toxicity was graded using the Radiation Therapy Oncology Group (RTOG) acute toxicity and RTOG/EORTC late toxicity scales. Results: A total of 67 women were enrolled with a median age of 49 years (range 31–69). Median follow-up was 25 months (range 11–34). Acute skin reactions included grade (G) 1 (n = 47, 70%), G2 (n = 10, 13%), and G3 (n = 1, 1.5%). Late skin toxicity was observed in 13 patients (19%), all of whom experienced G1 toxicity only. On multivariable analysis, diabetes mellitus was predictive of acute skin toxicity (p = 0.003), while age less than 50 years (p = 0.029) and diabetes mellitus (p = 0.013) were predictive of late skin toxicity. Conclusions: Whole breast irradiation with concomitant weekly boost appears feasible and safe. Further investigation is required to fully evaluate this schedule as an alternative to conventional whole breast irradiation with a sequential boost

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group

BACKGROUND AND PURPOSE: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results. MATERIALS AND METHODS: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint. RESULTS: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005). CONCLUSION: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer