Chemoradiotherapy

Chemoradiotherapy (CHRT) is often advocated for locally-advanced biliary tract cancer (LABTC). However there was not comparative study with chemotherapy alone (CH). Patients with hilar or extrahepatic non-metastatic, LABTC could be included in this phase II trial. The inclusion criteria required World Health Organisation (WHO) performance status ⩽ 2, bilirubinemia ⩽ 50 μM/L after biliary drainage if necessary, and possibility of external radiotherapy. Fluorouracil (5 FU) infusion and cisplatin, were given in association to radiotherapy (50 Gy) in the CHRT arm. Gemcitabine+oxaliplatin (GEMOX) was planned for 6 months in the CH arm. End-points were progression-free survival (PFS), overall survival (OS), toxicity and rate of biliary complications. The trial was closed before completion due to slow recruitment. Eighteen and 16 patients were included in the CHRT and CH arms, respectively. Median follow up was 27.9 months (± 2.8). Grade III-IV toxicities were mostly haematological (23% an...

To evaluate outcomes in prostate cancer patients classified as high-risk (HR) or very high-risk (VHR) who were treated with conformal radiation therapy (CRT) and androgen deprivation therapy (ADT). Between 11/2001 and 3/2012, 203 patients with HR disease received CRT to the prostate (78-82 Gy) and pelvic lymph nodes (46-50 Gy) with ADT (6 m-2 years). Median follow-up was 50 months (12 m-142 m). Biochemical failure was defined according to Phoenix definition. Imaging studies were used to identify local, regional or metastatic failure. Four different VHR/HR groupings were formed using the 2014 and revised 2015 NCCN guidelines. Differences were examined using Kaplan Meier (KM) estimates with log rank test and uni- and multivariate Cox regression analysis (MVA). Failure occurred in 30/203 patients (15%). Median time to failure was 30 m (4 m-76 m). KM estimate of 4 year biochemical disease free survival (b-DFS) for the entire cohort was 87% (95%CI: 82-92%). Four year KM survival estimate...

Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis. Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz fre...

Radiotherapy plays an essential role in the management of head and neck squamous cell carcinoma. Radiotherapy has a distinct advantage over surgical procedures in that it could achieve organ and function preservation with an efficacy similar to that of surgical series. To improve the clinical outcomes achievable by radiotherapy, altered fractionated radiotherapy has been prospectively tested for early and intermediate risk diseases, and was previously shown to be beneficial for local control and survival. Radiotherapy alone is insufficient for locally advanced disease; therefore, concurrent chemoradiotherapy is typically performed and plays an important role. A meta-analysis (Level Ia) revealed that the concurrent use of platinum agents appeared to improve tumor control and survival; however, this was accompanied by increases in the rates of both acute and late toxicities. Regarding radiation techniques, intensity modulated radiotherapy evolved in the 1990s, and has been globally us...

Planned neck dissection (ND) after radical chemoradiotherapy (CRT) for locally advanced nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. Thirty per cent of ND specimens show histological evidence of tumour. Consequently, a significant proportion of clinicians still practise planned ND. Fludeoxyglucose positron emission tomography (PET)-computerised tomography (CT) scanning demonstrated high negative predictive values for persistent nodal disease, providing a possible alternative paradigm to ND. Evidence is sparse and drawn mainly from retrospective single-institution studies, illustrating the need for a prospective randomised controlled trial. To determine the efficacy and cost-effectiveness of PET-CT-guided surveillance, compared with planned ND, in a multicentre, prospective, randomised setting. A pragmatic randomised non-inferiority trial comparing PET-CT-guided watch-and-wait policy with the current planned ND policy in HNSCC...

Traditional oncology distinguishes between two separate and incommensurable states in the evolution of solid malignancies: the localized disease, which is curable; and the disseminated status, which is per se palliative. Recently, a huge body of evidence suggests a fundamental change in the understanding of cancer, indicating an intermediate state in the trajectory of solid malignancies: the oligometastatic state. The following review will critically analyse existing hypotheses and facts from the basic sciences and try to contextualize it in regard to the clinical evidence available to date. Consecutively, it will try to draw possible clinical consequences for application of radiotherapy in this specific clinical scenario.

The diagnosis of carcinoma of unknown primary (CUP) is made after exclusion of the presence of a mucosal primary. There are two mains options for the primary treatment of CUP, either a neck node dissection followed by postoperative radiotherapy or chemo-radiotherapy, or a primary radiotherapy or chemo-radiotherapy depending on the nodal stage followed in case of residual neck disease by a selective neck dissection. There is no data to suggest the superiority of one over the other. For radiotherapy, unilateral neck or bilateral neck, including the upper aerodigestive tract mucosa are possible options. There is no definite data to demonstrate the superiority of one over the other, but owing the reduced toxicity of unilateral irradiation, and the possibility of salvage treatment in case of emergence of a mucosal primary and/or a contralateral neck node development, the former may be the preferred option. Advances in radiotherapy such as intensity modulated radiation therapy have the po...

The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The use of IMRT requires knowledge of the patterns of spreads and anatomy. Clinical trials demonstrate high variability in target delineation without specific guidance demonstrating the need for peer review and the use of a consensus atlas. Concomitant with radiation, fluorouracil bas...

Objective: To report acute hematological toxicity (HT) in patients receiving post-operative bowel sparing intensi- ty-modulated radiotherapy (IMRT) and cisplatin and its dosimetric predictors.
Methods: Clinical database of Phase III trial (NCT01279135), that randomized patients to post-operative conformal or intensity modulated radiation therapy, was searched to select patient strata that received bowel sparing IMRT (50 Gy/25#/5 wks) and concurrent cisplatin (40 mg m–2). Pelvic bone marrow (BM) was retrospectively delin- eated in two sets: whole bone (WB), and freehand (FH) inner cavity of bone. Dose volume histograms (DVH) of BM were obtained. Receiver operating characteristic (ROC) curve identi ed DVH thresholds that predicted for Grade≥ II HT with highest speci city. Univariate and multivariate analysis was performed.
Results: Overall 75 patients received concurrent cisplatin. Grades I–V HT was observed in 38.7%, 42.7%, 14.7%, 0%, and 0% patients, respectively. Grade ≥ II leuko- penia, neutropenia, anemia, and thrombocytopenia were observed in 26%, 40%, 26.5%, and 1.4% respec- tively. None of the HT resulted in treatment break. On univariate analysis, whole pelvis+ lumbar FH V30 >55% & V40>35%, whole pelvis WB and FH V40 > 35%, and lower pelvis WB and FH V40 >20% correlated for Grade ≥ II leucopenia and neutropenia. None of the BM dose volume constraints predicted for overall HT or neutro- penia on multivariate analysis.
Conclusion: The IMRT arm of NCT01279135 (PARCER study) that employed strict bowel constraints had unin- tentional but desirable BM sparing. None of the BM subvolume DVH parameters could be validated on multi- variate analysis.
advances in knowledge The prospective study reports feasibility of bone marrow sparing with bowel sparing post-operative pelvic IMRT and concurrent chemo- therapy for cervical cancer. The present study reports low incidence of hematological and gastrointestinal toxicity during post-operative chemoradiation with IMRT. As both whole bone and freehand pelvis BM contours predicted for HT, hence an easier method of whole bone contouring should continue to be used till further validation of more speci c BM subvolumes becomes available. The study results highlight the need for further research into dose volume constraints during post-operative IMRT.