Hyperfractionated Chemoradiotherapy Research Articles

Altered fractionation radiotherapy with or without chemotherapy in the treatment of head and neck cancer: a network meta-analysis.

ObjectivesA Bayesian network meta-analysis (NMA) was conducted in patients with head and neck cancers (HNCs) to estimate the efficacy and safety of treatment with conventional fractionation radiotherapy (CF), conventional fractionation chemoradiotherapy (CF_CRT), hyperfractionated radiotherapy (HF), hyperfractionated chemoradiotherapy (HF_CRT), accelerated fractionation radiotherapy, accelerated fractionation chemoradiotherapy, accelerated hyperfractionated radiotherapy (HART) or accelerated hyperfractionated chemoradiotherapy (HACRT) to identify superior treatments to aid in clinical decisions.MethodsPubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for potentially eligible randomized controlled trials up to December 2016. Overall survival (OS), disease-free survival (DFS) and locoregional control (LRC) were considered efficacy outcomes, whereas acute toxicity and late toxicity on skin and mucosa were considered safety outcomes. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment in each index.ResultsData from 72 trials with 21,868 participants were included in the analysis. Concerning OS, all treatments were associated with a significant advantage compared to CF alone, with HR effect sizes ranging from 0.64 to 0.83, and HACRT was significantly more effective than all the other treatments. The network comparisons of both HACRT vs HART and HF_CRT vs HF demonstrated a higher OS benefit, with an HR of 0.78 (95% credible interval [CrI]: 0.64–0.95) and 0.78 (95% CrI: 0.61–0.99), respectively. The results of SUCRA indicated that HACRT had the best ranking for OS and LRC, HF_CRT for DFS, HART for acute and late skin toxicity, CF_CRT for acute mucosal toxicity and HF_CRT for late mucosal toxicity.ConclusionThe NMA results support the notion that HACRT is the preferable treatment modality for HNCs because it has better rankings in all three efficacy indexes, although it does present a high risk of acute mucosal toxicity.

Post ASCO update 2016—lung cancer

The aim of this short review is to summarize the most important data relating to the field of thoracic tumors presented at the 2016 ASCO annual meeting. For small cell lung cancer (SCLC) the treatment algorithms once again remain unchanged. The CONVERT study was not able to show superiority of a modern chemoradiotherapy regimen using once daily fractionation over the historical standard of hyperfractionated chemoradiotherapy. With rovalpituzumab tesirine a promising new agent is in development, leading to encouraging treatment results in patients with pretreated, extensive SCLC disease on phase IB level. Regarding nonsmall cell lung cancer (NSCLC) a phase II trial was able to confirm high efficacy of the combination dabrafenib/trametinib if a BRAF-V600E mutation is detectable. These data should lead to more widespread implementation of BRAF mutation testing in routine diagnostic work-up. In the J‑ALEX trial alectinib outperformed crizotinib in the first-line treatment of Asian patients with ALK-rearranged metastatic NSCLC. However, further data from ongoing studies will be necessary to better define the optimal sequencing of treatments for this genetically defined subgroup of patients.

Concurrent hyperfractionated chemoradiotherapy for head and neck squamous cell carcinoma: the prognostic impact of the overall treatment time and completion rates of chemotherapy.

The purpose of this study was to investigate whether the overall treatment time and completion rates of chemotherapy were predictive factors for the survival rates in patients with squamous cell carcinoma of the head and neck (SCCHN) who were treated with concurrent chemoradiotherapy (CCRT) using hyperfractionated radiotherapy (RT) and daily carboplatin. The number of intermission days of RT were as follows; 0 (n = 37), 1–5 (n = 8), 6–10 (n = 12) and ≥11 (n = 12), and the days of RT without carboplatin; 0 (n = 27), 1–5 (n = 13), 6–10 (n = 13) and ≥7 (n = 16). The overall treatment time (≤48 vs ≥49 days) was a significant prognostic factor for the local control, disease-free survival and overall survival rates. The completion rate of chemotherapy, as the number of days of RT without carboplatin, was not a significant factor affecting any of the survival rates. In discussion, the strengths of the present study contain that all the patients were treated with 72 Gy delivered as 1.2 Gy twice daily, and received concurrent chemotherapy comprising daily carboplatin as a radio-sensitizer. Based on the results, the completion rate of chemotherapy may have a lower impact on the local control rate in comparison with the overall treatment time. We believe that when a treatment interruption is needed because of the acute toxicities, hyperfractionated RT should be resumed as soon as possible independently while continuing the break of daily carboplatin. The overall treatment time influenced the clinical outcomes in SCCHN patients treated with hyperfractionated CCRT using carboplatin, while the impact of the completion rates of daily carboplatin was limited. Sixty-nine consecutive patients with SCCHN were initially treated with definitive CCRT and were retrospectively analyzed. All 69 patients were treated with CCRT using hyperfractionated RT of 72 Gy in 60 fractions and daily carboplatin (25 mg/m2). The patients treated with other chemotherapeutic regimens or induction chemotherapy were excluded. On the intermission days of the RT, carboplatin was not prescribed. After the intermission, CCRT using RT plus daily carboplatin or RT alone was resumed.

Phase II Trial of a Trimodality Regimen for Stage III Non–Small-Cell Lung Cancer Using Chemotherapy As Induction Treatment With Concurrent Hyperfractionated Chemoradiation With Carboplatin and Paclitaxel Followed by Subsequent Resection: A Single-Center Study

PURPOSE We started a phase II trial of induction chemotherapy and concurrent hyperfractionated chemoradiotherapy followed by either surgery or boost chemoradiotherapy in patients with advanced, stage III disease. The purpose is to achieve better survival in the surgery group with minimum morbidity and mortality. PATIENTS AND METHODS Patients treated from 1998 to 2002 with neoadjuvant chemoradiotherapy and surgical resection for stage III NSCLC were analyzed. The treatment consisted of four cycles of induction chemotherapy with carboplatin/paclitaxel followed by chemoradiotherapy with a reduced dose of carboplatin/paclitaxel and accelerated hyperfractionated radiotherapy with 1.5 Gy twice daily up to 45 Gy. After restaging, operable patients underwent thoracotomy. Inoperable patients received chemoradiotherapy up to 63 Gy. Study end points included resectability, pathologic response, and survival. Results One hundred twenty patients were enrolled; 25% patients had stage IIIA, 73% had stage IIIB, and 2% stage IV. After treatment, 47.5% had downstaging, 29.2% had stable disease, and 23.3% had progressive disease. Thirty patients (25%) were not eligible for operation because of progressive disease, stable disease, and/or functional deterioration with one treatment-related death. The 30-day mortality was 5% in patients who underwent operation. The 5-year survival rate for 120 patients was 21.7%, and it was 43.1% in patients with complete resection. In postoperative patients with stage N0 disease, 5-year survival was 53.3%; if stage N2 or N3 disease was still present, 5-year survival was 33.3%. CONCLUSION Staging and treatment with chemoradiotherapy and complete resection performed in experienced centers achieve acceptable morbidity and mortality.

Comprehensive Mediastinal Nodal Characterization Optimizes Outcome Prediction: Results From a Single-institution Trimodality Regimen in Mediastinoscopy-Defined Stage III Non-Small Cell Lung Cancer (NSCLC)

Purpose/Objective(s): To report our experience with a trimodality approach to mediastinoscopy-defined stage III NSCLC. Materials/Methods: Following pre-treatment evaluation, our institutional protocols have consisted of neoadjuvant accelerated hyperfractionated chemoradiotherapy (AHFX-ChRT), followed by curative resection, followed by adjuvant AHFX-ChRT. AHFX-ChRT consisted of 30Gy/20fx at 1.5Gy/fx BID (> 6h interfraction interval). Chemotherapy consisted of cisplatin/paclitaxel or carboplatin/paclitaxel. Pretreatment evaluation included history and physical exam, heme and chemistry profiles, pulmonary function tests, computed tomography of chest and upper abdomen, positron emission tomography (PET), bronchoscopy, and mediastinoscopy (meds). Results: Between 2/99 and 1/05, a total of 121 patients (pts) with pathologically confirmed NSCLC were treated in a similar fashion. The study sample consists of 78 (64.5%) males and 43 (35.5%) females with a median age of 61 years (range 31-78). The median Karnofsky performance status (KPS) was 90 (range 70100). 47.9% and 21.5% of pts had adenocarcinoma and squamous cell carcinoma, respectively (resp). 57.9% of pts had right-sided tumor. Meds-defined stage was IIIA in 57.9%, IIIB in 31.4%, other in 5.8%; 6 pts did not undergo meds. 100 pts (82.6%) completed neoadjuvant AHFX-ChRT and curative resection (pneumonectomy was performed in 29 pts). There were 4 postoperative deaths (4%). Pathologic complete response (pCR) was noted in the primary in 21% and 41% in the nodes; pCR in both was 16%. Overall, 72 pts (72%) completed the protocol as above. The median follow-up for these pts is 27.7 mos. Median survival time (MST) and 2-year OS were 29.9 mos and 63.5%, resp. 2-year LC rate and 2-year metastaticfree survival were 85.2% and 70.3%, resp. For pts with meds-defined stage IIIA and stage IIIB disease, MST was 34.5 mos and 26 mos; 2-year OS was 69% and 50.3%, resp (p=NS). For pts with pCR in the nodes, more than half were still alive at the time of analysis while those with residual nodal disease had a MST of 28.8 mos; 2-yr OS was 70.8% versus 60.2%, resp (p=0.0079). On univariate analysis, KPS (analyzed as a continuous variable), absence of PET positive nodal stations, pCR in the nodes, and percentage of nodes positive at resection (analyzed as a continuous variable) were prognostic for OS. On multivariate analysis (MVA), KPS and absence of PET positive nodal stations remained significant. Mediastinal stage, pCR in the primary, margin status, age, sex, histology, side of tumor, number of mediastinal positive stations (none versus single versus multiple), and type of curative resection (pneumonectomy versus other) did not correlate with OS. Percentage of nodes positive at resection and sex (female versus male) were significantly correlated with local control on MVA. Percentage of nodes positive at resection was the only factor significantly correlated with metastatic-free survival on MVA. Conclusions: This protocol employing neoadjuvant AHFX-ChRT followed by curative resection and adjuvant AHFX-ChRT is feasible and effective, comparing favorably with previously reported data for mediastinoscopy-defined stage III NSCLC. Comprehensive mediastinal nodal characterization optimizes outcome prediction.

P-56 Early concurrent normo- and hyperfractionated chemoradiotherapy in limited small cell lung cancer (LSCLC). Experience with 34 treated patients

P-56 Early concurrent normo- and hyperfractionated chemoradiotherapy in limited small cell lung cancer (LSCLC). Experience with 34 treated patients