Prostate Stereotactic Ablative Radiation Therapy Using Volumetric Modulated Arc Therapy to Dominant Intraprostatic Lesions

PurposeTo investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal tissue complication probability (NTCP).Methods and MaterialsTen prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV) prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTVProstate prescription, and PTVDIL prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively.ResultsWhen treating the prostate alone, the median PTVDIL prescription was 125% (range: 110%-140%) of the PTVProstate prescription. Median PTVDIL D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTVDIL prescriptions and similar PTVDIL median doses were possible when including the proxSV within the prescription. TCP depended on prostate α/β ratio and was highest with an α/β ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm3 of rectum (Dmax0.5cc), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions.ConclusionsBoosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax0.5cc. If the α/β ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting

NEOSCOPE: A randomized phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma

Background: Oxaliplatin-capecitabine (OxCap) and carboplatin-paclitaxel (CarPac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer. Patients and methods: A non-blinded, randomised (1:1 via a centralised computer system), ‘pick a winner’ phase II trial. Patients with resectable oesophageal adenocarcinoma ≥ cT3 and/or ≥ cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m2 day 1, 15, 29; capecitabine 625 mg/m2 bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 day 1, 8, 15, 22, 29). Radiotherapy dose was 45 Gy/25 fractions/5 weeks. Both arms received induction OxCap chemotherapy (2 × 3 week cycles of oxaliplatin 130 mg/m2 day 1, capecitabine 625 mg/m2 bd days 1–21). Surgery was performed 6–8 weeks after nCRT. Primary end-point was pathological complete response (pCR). Secondary end-points included toxicity, surgical morbidity/mortality, resection rate and overall survival. Statistics: Based on pCR ≤ 15% not warranting future investigation, but pCR ≥ 35% would, 76 patients (38/arm) gave 90% power (one-sided alpha 10%), implying that arm(s) having ≥10 pCR out of first 38 patients could be considered for phase III trials. ClinicalTrials.gov: NCT01843829. Funder: Cancer Research UK (C44694/A14614). Results: Eighty five patients were randomised between October 2013 and February 2015 from 17 UK centres. Three of 85 (3.5%) died during induction chemotherapy. Seventy-seven patients (OxCapRT = 36; CarPacRT = 41) underwent surgery. The 30-d post-operative mortality was 2/77 (2.6%). Grade III/IV toxicity was comparable between arms, although neutropenia was higher in the CarPacRT arm (21.4% versus 2.6%, p = 0.01). Twelve of 41 (29.3%) (10 of first 38 patients) and 4/36 (11.1%) achieved pCR in the CarPacRT and OxcapRT arms, respectively. Corresponding R0 resection rates were 33/41 (80.5%) and 26/36 (72.2%), respectively. Conclusion: Both regimens were well tolerated. Only CarPacRT passed the predefined pCR criteria for further investigation

Developing a class solution for Prostate Stereotactic Ablative Body Radiotherapy (SABR) using Volumetric Modulated Arc Therapy (VMAT)

Background and purpose To develop a class solution for prostate Stereotactic Ablative Radiotherapy (SABR) using Volumetric Modulated Arc Therapy (VMAT). Materials and methods Seven datasets were used to compare plans using one 360° arc (1FA), one 210° arc (1PA), two full arcs and two partial arcs. Subsequently using 1PA, fifteen datasets were compared using (i) 6 mm CTV–PTV margins, (ii) 8 mm CTV–PTV margins and (iii) including the proximal SV within the CTV. Monaco™ 3.2 (Elekta™) was used for planning with the Agility™ MLC system (Elekta™). Results Highly conformal plans were produced using all four arc arrangements. Compared to 1FA, 1PA resulted in significantly reduced rectal doses, and monitor units and estimated delivery times were reduced in six of seven cases. Using 6 mm CTV–PTV margins, planning constraints were met for all fifteen datasets. Using 8 mm margins required relaxation of the uppermost bladder constraint in three cases to achieve adequate coverage, and, compared to 6 mm margins, rectal and bladder doses significantly increased. Including the proximal SV required relaxation of the uppermost bladder and rectal constraints in two cases, and rectal and bladder doses significantly increased. Conclusions Prostate SABR VMAT is optimal using 1PA. 6 mm CTV–PTV margins, compatible with daily fiducial-based IGRT, are consistently feasible in terms of target objectives and OAR constraints

Effective treatment of anal cancer in the elderly with low-dose chemoradiotherapy

Chemoradiotherapy (CRT) is accepted as the standard initial treatment for squamous cell anal cancer. However, frail elderly patients cannot always tolerate full-dose CRT. This paper reports the results of a modified regimen for this group of patients. In all, 16 patients with biopsy-proven squamous cell carcinoma of the anal canal or margin and performance status or co-morbidity precluding the use of full-dose CRT were included in this protocol. The median age was 81 (range 77–91). Patients received a dose of 30 Gy to the gross tumour volume plus 3 cm margin in all directions. Concurrent chemotherapy comprised 5-fluorouracil 600 mg m−2 given over 24 h on days 1–4 of radiotherapy. The treatment was well tolerated. All 16 patients completed treatment as planned. Only one patient experienced any grade 3 toxicity (skin). The local control at a median follow-up of 16 months was 73% (13 out of 16). The overall survival was 69% and disease-specific survival 86%. This is a well-tolerated regimen for elderly/poor performance patients with anal cancer, which can achieve high rates of local control and survival. Longer follow-up will determine whether these encouraging results are maintained

Can we <i>S</i>ave the rectum by watchful waiting or <i>T</i>rans<i>A</i>nal microsurgery following (chemo) <i>R</i>adiotherapy versus total mesorectal excision for early <i>RE</i>ctal <i>C</i>ancer (STAR-TREC study)?::protocol for a multicentre, randomised feasibility study

Introduction Total mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery. Methods and analysis STAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2