Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial (original) (raw)

Comparing Oncologic Outcomes and Toxicity for Combined Modality Therapy vs. Carbon-Ion Radiotherapy for Previously Irradiated Locally Recurrent Rectal Cancer

Cancers

No standard treatment paradigm exists for previously irradiated locally recurrent rectal cancer (PILRRC). Carbon-ion radiotherapy (CIRT) may improve oncologic outcomes and reduce toxicity compared with combined modality therapy (CMT). Eighty-five patients treated at Institution A with CIRT alone (70.4 Gy/16 fx) and eighty-six at Institution B with CMT (30 Gy/15 fx chemoradiation, resection, intraoperative electron radiotherapy (IOERT)) between 2006 and 2019 were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), distant metastasis (DM), or any disease progression (DP) were analyzed with the Kaplan–Meier model, with outcomes compared using the Cox proportional hazards model. Acute and late toxicities were compared, as was the 2-year cost. The median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 and 2.6 years, respectively (p ≤ 0.01). No difference was seen in the cumulative incidence of PR (p = 0.17), DM (p = 0.39), ...

Re-irradiation in recurrent rectal cancer: single institution experience

Translational Gastrointestinal Cancer, 2014

To determine the rates of acute and late toxicity, the efficacy to relieve symptoms, progression free survival, and over all survival in rectal cancer patients treated with re-irradiation. Patients and methods: Between June 2009 and December 2012, 32 patients with recurrent rectal cancer previously treated with pelvic irradiation, were treated with 180 cGy/fraction, with a total dose 39 Gy if the treatment interval ≥1 year, and 30 Gy if interval <1 year. The dose was delivered to planning target volume (PTV) including gross target volume plus 2-3 cm margin. Concurrent chemotherapy was administrated in first five days of radiotherapy. Patients were evaluated during and after completion of treatment for acute, late toxicity, and response. Results: Re-irradiation was well tolerated, no grade 4 toxicity was recorded, most toxicities were mild (grade 1-2), only 6.2% developed grade 3 acute gastrointestinal and 6.2% developed grade 3 late skin toxicity. Symptoms were effectively palliated, bleeding was relieved in 100%, and 80% recovered of pain symptoms. Two years rates of progression free survival and overall survival were 21% and 38% respectively. Interval to reirradiation, previous radiation dose, and total radiation dose showed significant relation with overall survival. Conclusions: Re-irradiation in recurrent rectal cancer was well tolerated with mild rates of acute and late toxicities. Bleeding and pain were well controlled.

Comparison of different external beam treatment techniques to deliver high-dose irradiation to local recurrent rectal carcinoma

Tumori

Treatment of local-regional recurrent rectal carcinoma is a challenging problem, and local control may be dose dependent; doses should probably exceed 60 Gy. Our aim was to verify the possibility to deliver 66 Gy to the target, but less than 35 Gy to the small bowel, comparing different 3D irradiation techniques, in a selected group of patients. Five patients with local recurrent rectal carcinoma were selected as representative of different presentations of the disease. Gross tumor volume and clinical target volume were defined [by RS]. Tumors ranged between 182 and 540 cc, and small bowel volumes between 748 and 1050 cc. A three-field technique, coplanar multiple fields, noncoplanar fields and a proton beam were compared using dose volume histograms. A positive result was scored when > or = 90% of the target received the prescribed dose with no more than 5% of the small bowel receiving more than 35 Gy. Doses were escalated in steps of 2 Gy from 60 to 66 Gy. The number of plans f...

Advances in Radiotherapy in Operable Rectal Cancer

Digestive Surgery, 2009

rent long-course chemoradiotherapy. As survival is only marginally affected despite low local recurrence, future trials should aim to address metastatic disease. End points which incorporate function and quality of life must be used.

Comparison of dosimetries of carbon-ion pencil beam scanning, proton pencil beam scanning and volumetric modulated arc therapy for locally recurrent rectal cancer

Journal of Radiation Research, 2022

We compared the dose distributions of carbon-ion pencil beam scanning (C-PBS), proton pencil beam scanning (P-PBS) and Volumetric Modulated Arc Therapy (VMAT) for locally recurrent rectal cancer. The C-PBS treatment planning computed tomography (CT) data sets of 10 locally recurrent rectal cancer cases were randomly selected. Three treatment plans were created using identical prescribed doses. The beam angles for C-PBS and P-PBS were identical. Dosimetry, including the dose received by 95% of the planning target volume (PTV) (D95%), dose to the 2 cc receiving the maximum dose (D2cc), organ at risk (OAR) volume receiving > 15Gy (V15) and > 30Gy (V30), was evaluated. Statistical significance was assessed using the Wilcoxon signed-rank test. Mean PTV-D95% values were > 95% of the volume for P-PBS and C-PBS, whereas that for VMAT was 94.3%. However, PTV-D95% values in P-PBS and VMAT were < 95% in five and two cases, respectively, due to the OAR dose reduction. V30 and V15 to the rectum/intestine for C-PBS (V30 = 4.2 ± 3.2 cc, V15 = 13.8 ± 10.6 cc) and P-PBS (V30 = 7.3 ± 5.6 cc, V15 = 21.3 ± 13.5 cc) were significantly lower than those for VMAT (V30 = 17.1 ± 10.6 cc, V15 = 55.2 ± 28.6 cc). Bladder-V30 values with P-PBS/C-PBS (3.9 ± 4.8 Gy(RBE)/3.0 ± 4.0 Gy(RBE)) were significantly lower than those with VMAT (7.9 ± 8.1 Gy). C-PBS provided superior dose conformation and lower OAR doses compared with P-PBS and VMAT. C-PBS may be the best choice for cases in which VMAT and P-PBS cannot satisfy dose constraints. C-PBS could be another choice for cases in which VMAT and P-PBS cannot satisfy dose constraints, thereby avoiding surgical resection.

Overview of Radiation Therapy for Treating Rectal Cancer

Annals of Coloproctology, 2014

A major outcome of importance for rectal cancer is local control. Parallel to improvements in surgical technique, adjuvant therapy regimens have been tested in clinical trials in an effort to reduce the local recurrence rate. Nowadays, the local recurrence rate has been reduced because of both good surgical techniques and the addition of radiotherapy. Based on recent reports in the literature, preoperative chemoradiotherapy is now considered the standard of care for patients with stages II and III rectal cancer. Also, short-course radiotherapy appears to pro vide effective local control and the same overall survival as more long-course chemoradiotherapy schedules and, therefore, may be an appropriate choice in some situations. Capecitabine is an acceptable alternative to infusion fluorouracil in those patients who are able to manage the responsibilities inherent in self-administered, oral chemotherapy. However, concurrent administration of oxaliplatin and radiotherapy is not recommended at this time. Radiation therapy has long been considered an important adjunct in the treatment of rectal cancer. Although no prospective data exist for several issues, we hope that in the near future, patients with rectal cancer can be treated by using the best combination of surgery, radiation therapy, and chemotherapy in near future.

A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer (APHRODITE): protocol for a multicentre, open-label randomised controlled trial

BMJ Open

IntroductionThe standard of care for patients with localised rectal cancer is radical surgery, often combined with preoperative neoadjuvant (chemo)radiotherapy. While oncologically effective, this treatment strategy is associated with operative mortality risks, significant morbidity and stoma formation. An alternative approach is chemoradiotherapy to try to achieve a sustained clinical complete response (cCR). This non-surgical management can be attractive, particularly for patients at high risk of surgical complications. Modern radiotherapy techniques allow increased treatment conformality, enabling increased radiation dose to the tumour while reducing dose to normal tissue. The objective of this trial is to assess if radiotherapy dose escalation increases the cCR rate, with acceptable toxicity, for treatment of patients with early rectal cancer unsuitable for radical surgery.Methods and analysisAPHRODITE (A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rec...