A surveillance study of patterns of reirradiation practice using external beam radiotherapy in Japan

The aim of this study was to survey the present status and patterns of reirradiation (Re-RT) practice using external beam radiotherapy in Japan. We distributed an e-mail questionnaire to the Japanese Society for Radiation Oncology partner institutions, which consisted of part 1 (number of Re-RT cases in 2008–2012 and 2013–2018) and part 2 (indications and treatment planning for Re-RT and eight case scenarios). Of the 85 institutions that replied to part 1, 75 (88%) performed Re-RTs. However, 59 of these 75 institutions (79%) reported difficulty in obtaining Re-RT case information from their databases. The responses from 37 institutions included the number of Re-RT cases, which totaled 508 in the period from 2009 to 2013 (institution median 3; 0–235), and an increase to 762 cases in the period from 2014 to 2018 (12.5; 0–295). A total of 47 physicians responded to part 2 of the survey. Important indications for Re-RT that were considered were age, performance status, life expectancy, absence of distant metastases and time interval since previous radiotherapy. In addition to clinical decision-making factors, previous total radiation dose, volume of irradiated tissue and the biologically equivalent dose were considered during Re-RT planning. From the eight site-specific scenarios presented to the respondents, >60% of radiation oncologists agreed to perform Re-RT. Re-RT cases have increased in number, and interest in Re-RT among radiation oncologists has increased recently due to advances in technology. However, several problems exist that emphasize the need for consensus building and the establishment of guidelines for practice and prospective evaluation.     

Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be a phantom tumor phenomenon

Some nasopharyngeal carcinoma (NPC) patients may present convincing radiological evidence mimicking residual or recurrent tumor after radiotherapy. However, by means of biopsies and long term follow-up, the radiologically diagnosed residuals/recurrences are not always what they appear to be. We report our experience on this “phantom tumor” phenomenon. This may help to avoid the unnecessary and devastating re-irradiation subsequent to the incorrect diagnosis.In this longitudinal cohort study, we collected 19 patients of image-based diagnosis of residual/recurrent NPC during the period from Feb, 2010 to Nov. 2016, and then observed them until June, 2019. They were subsequently confirmed to have no residual/recurrent lesions by histological or clinical measures. Image findings and pathological features were analyzed.Six patients showed residual tumors after completion of radiotherapy and 13 were radiologically diagnosed to have recurrences based on magnetic resonance imaging (MRI) criteria 6 to 206 months after radiotherapy. There were 3 types of image patterns: extensive recurrent skull base lesions (10/19); a persistent or residual primary lesion (3/19); lesions both in the nasopharynx and skull base (6/19). Fourteen patients had biopsy of the lesions. The histological diagnoses included necrosis/ inflammation in 10 (52.7%), granulation tissue with inflammation in 2, and reactive epithelial cell in 1. Five patients had no pathological proof and were judged to have no real recurrence/residual tumor based on the absence of detectable plasma EB virus DNA and subjective judgment. These 5 patients have remained well after an interval of 38–121 months without anti-cancer treatments.Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be unreliable. False positivity, the “phantom tumor phenomenon”, is not uncommon in post-radiotherapy MRI. This is particularly true if the images show extensive skull base involvement at 5 years or more after completion of radiotherapy. MRI findings compatible with NPC features must be treated as a real threat until proved otherwise. However, the balance between under- and over-diagnosis must be carefully sought. Without a pathological confirmation, the diagnosis of residual or recurrent NPC must be made taking into account physical examination results, endoscopic findings and Epstein-Barr virus viral load. A subjective medical judgment is needed based on clinical and laboratory data and the unique anatomic complexities of the nasopharynx.     

Decision making in the management of recurrent head and neck cancer

Despite substantial improvements in head and neck squamous cell carcinoma (HNSCC) treatment, the major obstacle to long‐term survival remains disease recurrence. Salvage options are often limited due to prior therapy and the escalated morbidity of retreatment. The costs of treatment must be measured against the anticipated quality and quantity of life recovered, even with resectable disease. This review surveys the recurrent HNSCC literature to better guide decision making. Across multiple studies, negative prognostic factors include impaired performance status, advanced recurrent stage, brief disease‐free interval, previous chemotherapy, and nonlaryngeal sites of recurrence. When possible, surgical salvage remains the principal option for durable disease control, quality of life preservation, and cure. Nonsurgical therapies have also demonstrated measurable improvements in locoregional control. Interpretation of salvage literature must be tempered by recognition of significant selection bias. The decision for salvage therapy must be individualized, with management that involves well‐informed patients resulting in the best outcomes. © 2013 Wiley Periodicals, Inc. Head Neck 36 : 144–151, 2014     

再放疗并同步使用Docetaxel在鼻咽癌放疗后复发病人中的应用

目的:不能手术切除的鼻咽癌放疗后再复发的病人,其治疗困难,化疗疗效差,而单独再放疗只能挽救一小部分病人,本文探讨再放疗并同步使用多西紫彬醇(Docetaxel)在鼻咽癌首次放疗后复发病人中可行性及毒副反应,并评价其疗效。方法:对11例鼻咽癌足量放疗后经组织病理学证实复发、而无法行手术及腔内放疗的患者进行了同步放化疗。放疗采用三维适形放疗,外照射鼻咽部,分次量为1.8Gy,总剂量为36Gy-39.6Gy。化疗采用Docetaxel,15mg/m2,每周一次,静脉滴注。结果:10%、33%的患者分别出现Ⅲ度、Ⅳ度皮肤反应,18%、10%的病人分别出现Ⅲ度、Ⅳ度黏膜反应,18%患者出现Ⅲ度恶心呕吐,27%的患者出现Ⅲ度-Ⅳ度白细胞下降,10%患者出现Ⅲ度血小板下降。1例患者因严重的黏膜反应致使治疗延迟2周。治疗结束后,9例(82%)患者达到CR,2例(18%)达到PR,反应率为100%。结论:对于放疗后局部复发的鼻咽癌患者,采用同步放化疗,3D-CRT同时每周使用Docetaxel是可行的,其毒性反应在可以接受的范围内,短期疗效显著。     

复发鼻咽癌临床研究进展

局部复发鼻咽癌的治疗对放射肿瘤学家而言是一项挑战.再程放疗虽然仍是复发鼻咽癌治疗的主要手段,但是,相关的有效临床资料十分缺乏.本文就近年来有关复发鼻咽癌治疗的文献描述进行复习,对其复发因素和诊断的临床特征、不同的放疗手段,如常规放疗、立体定向放疗、近距离治疗、三维适形放疗、调强放疗或几种手段的综合治疗的现状作一综述.     

Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck

BACKGROUND: Our objectives were to determine the incidence of acute and late toxicities and to estimate the 2-year overall survival for patients treated with reirradiation and chemotherapy for unresectable squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field were eligible. Four weekly cycles of 5-fluorouracil 300 mg/m2 IV bolus and hydroxyurea 1.5 g by mouth were used with 60 Gy at 1.5 Gy twice-daily fractions. Toxicity was scored according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. RESULTS: Seventy-nine of the 86 patients enrolled were analyzable. The worst acute toxicity was grade 4 in 17.7% and grade 5 in 7.6%. Grade 3 and 4 late toxicities were found in 19.4% and 3.0%, respectively. The estimated cumulative incidence of grade 3 to 4 late effects occurring at >1 year was 9.4% (95% confidence interval [CI]: 0, 19.7) at 2 and 5 years. The 2- and 5-year cumulative incidence for grade 4 toxicity was 3.1% (95% CI: 0, 9.3). The estimated 2- and 5-year survival rates were 15.2% (95% CI: 7.3, 23.1) and 3.8% (95% CI: 0.8, 8.0), respectively. Patients who entered the study at >1 year from initial radiotherapy (RT) had better survival than did those who were <1 year from prior RT (median survival, 9.8 months vs 5.8 months; p = .036). No correlation was detected between dose received and overall survival. Three patients were alive at 5 years. CONCLUSION: This is the first prospective multi-institutional trial testing reirradiation plus chemotherapy for recurrent or second SCCHN. The approach is feasible with acceptable acute and late effects. The results serve as a benchmark for ongoing RTOG trials.     

Re-Irradiation for Locally Recurrent Lung Cancer: A Single Center Retrospective Analysis

The treatment of locally recurrent lung cancer is a major challenge for radiation-oncologists, especially with data on high-dose reirradiation being limited to small retrospective studies. The aim of the present study is to assess overall survival (OS) for patients with locally recurrent lung cancer after high-dose thoracic reirradiation. Thirty-nine patients who were re-irradiated for lung cancer relapse between October 2013 and February 2019 were eligible for the current retrospective analysis. All patients were re-irradiated with curative intent for in-field tumor recurrence. The diagnostic work-up included a mandatory ¹⁸F-FDG-PET-CT scan and—if possible—histological verification. The ECOG was ≤2, and the interval between initial and second radiation was at least nine months. Thirty patients (77%) had non-small cell lung cancer (NSCLC), eight (20%) had small cell lung cancer (SCLC), and in one patient (3%) histological confirmation could not be obtained. More than half of the patients (20/39, 51%) received re-treatment with dose differentiated accelerated re-irradiation (DART) at a median interval of 20.5 months (range: 6–145.3 months) after the initial radiation course. A cumulative EQD₂ of 131 Gy (range: 77–211 Gy) in a median PTV of 46 mL (range: 4–541 mL) was delivered. Patients with SCLC had a 3 mL larger median re-irradiation volume (48 mL, range: 9–541) compared to NSCLC patients (45 mL, range: 4–239). The median cumulative EQD2 delivered in SCLC patients was 84 Gy (range: 77–193 Gy), while NSCLC patients received a median cumulative EQD2 of 135 Gy (range: 98–211 Gy). The median OS was 18.4 months (range: 0.6–64 months), with tumor volume being the only predictor (p < 0.000; HR 1.007; 95%-CI: 1.003–1.012). In terms of toxicity, 17.9% acute and 2.6% late side effects were observed, with a toxicity grade >3 occurring in only one patient. Thoracic high dose reirradiation plays a significant role in prolonging survival, especially in patients with small tumor volume at recurrence.