The Development of an Umbrella Trial (PLATO) to Address Radiation Therapy Dose Questions in the Locoregional Management of Squamous Cell Carcinoma of the Anus

Abstract

Purpose/Objective(s): Liver transplant, the gold standard treatment for most Hepatocellular carcinomas (HCC), was till recently not being considered as an option in patients having portal vein tumor thrombus (PVTT). These patients were offered only palliative treatments like Radio frequency ablation (RFA), Trans-arterial chemo-embolization (TACE) and conventional external beam radiation therapy (EBRT). With advent of SBRT, precise targeting and motion management has improved local control, making it possible to offer curative liver transplant post SBRT (Stereotactic Body Radiation therapy) to these cases where transplant was ruled out in the past. Materials/Methods: We present 48 of our cases, initially considered unfit for transplant and referred for SBRT to PVTT alone or with HCC lesion from April 2011 till November 2015. Adequate respiratory motion management with either deep inspiratory breath hold (DIBH) or synchrony respiratory tracking was used in all cases. Post SBRT, cases were assessed at 4, 8 and 12 weeks for transplant feasibility. Plan details and follow up data was analyzed with primary end point as amenability to liver transplant. Results: Intent of treatment was curative in 32 (66.6%) cases with limited disease and palliative in remaining 16 (33.3%) cases. Of all the cases, 38 (79%) had multi centric disease and 34 cases (70.8%) had received alternative multimodality treatment in past, before SBRT. Based on Japan cancer group classification 12.5% (n Z 6), 25% (n Z 12), 22.9% (n Z 11) and 39.5% (n Z 19) cases had Vp1, Vp2, Vp3 and Vp4 type PVTT, respectively. Twenty cases (42%) were treated on robotic radiosurgery and 28 cases (58%) on Linac with DIBH. Most frequent dose fractionation used was 60 Gy (range 25 -60 Gy) in 5 fractions (range 3-20 fr). Treatment was well tolerated with mild nausea and fatigue being the most common side effect with no RTOG grade 3 or more toxicity reported. At the time of analyses, amongst 32 curative cases, 23 (71.9%) were alive while 6 (18.8%) had expired and 3 (9.3%) were lost to follow up. Eleven (34.3% of 32 curative) cases underwent successful transplant, 2-3 months post SBRT while 5 (15.6%) are awaiting response assessment. Remaining 2 (6.2%) cases are living with stable disease and 5 (15.6%) with systemic progression. Amongst 16 palliative cases, 7 (43.75%) were still alive, 4 cases (25%) lost to follow up and 5 (31.25%) had expired. Median survival was 13 months in all 48 cases and 26 months (range 8-46 months) for transplant cases. Conclusion: Presence of PVTT is no longer considered a contraindication to liver transplant. Adequately selected cases can be offered SBRT as single modality or as a part of multimodality regime. With growing data from well-designed future studies, PVTT-SBRT promises to improve outcomes in selected HCC cases by making them amenable to liver transplant. SBRT-PVTT therefore merits attention for its potential as an integral part of multidisciplinary treatment approach towards inoperable HCC, realizing the unmet need of adequate local c...

Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma

“…These are also in keeping with the ongoing PLATO trial. 43 The IMRT guidance was developed in the run up to the PLATO trial, which is a platform of studies for ASCC using the UK IMRT guidance as a backbone for RT delivery. The patterns of recurrence reported here support the rationale of the ACT5 trial.…”

Management of anal cancer patients – a pattern of care analysis in German-speaking countries

“…As reflected in the different guidelines (ESMO-ESSO-ESSO, UK, Australasian, NCCN) [6][7][8][9], we observed a rather large variability in the RT doses used for the primary tumor, as well as for involved and elective lymph nodes among the different Germanspeaking institutions. The ongoing PLATO umbrella trial, containing the ACT3, ACT4 and ACT5 trial, currently assesses the efficacy and toxicity of riskadapted RT in ASCC [22]. ACT3 is a nonrandomized phase II trial for patients with T1N0 tumors after local resection.…”

Early-stage Favourable Anal Cancer: A Retrospective Analysis of Clinical Outcomes of a Moderately Low Dose Elective Nodal Intensity-modulated Radiotherapy Schedule

“…Excellent local control and disease-free survival rates have been observed using low dose (30 Gy in 15 fractions) involved-field chemoradiotherapy regimens in patients with residual microscopic or very small volume tumours [11]. Interesting data on this issue are expected in the future from the results of the forthcoming ACT4 PLATO (PersonaLising Anal cancer radioTherapy dOse) trial exploring prospectively in patients with early disease up to 4 cm the role of dose de-escalation radiotherapy to the anal tumour (41.4 Gy in 23 fractions) and to the elective nodal regions (34.5 Gy in 23 fractions, similar to the prophylactic radiotherapy dose used in our study) [24].…”