Predictors of toxicity after curative reirradiation with intensity modulated radiotherapy or proton therapy for recurrent head and neck carcinoma: new dose constraints for pharyngeal constrictors muscles and oral cavity.

BACKGROUND: Our study aims to identify predictive factors of moderate to severe (grade ≥ 2) late toxicity after reirradiation (reRT) of recurrent head and neck carcinoma (HNC) and explore the correlations between dose organs at risk (OAR) and grade ≥ 2 toxicity. MATERIAL AND METHODS: Between 09/2007 and 09/2019, 55 patients were re-irradiated with IMRT or proton therapy with curative intent for advanced HNC. Our study included all patients for whom data from the first and second irradiations were available. Co-variables, including interval to reRT, size of re-irradiated PTV, and dose to OAR, were analyzed as potential predictors for developing moderate to severe long-term toxicity with death as a competing risk. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. RESULTS: Twenty-three patients participated in our study. After a median follow-up of 41 months, 65% of the patients experienced grade ≥ 2 late toxicity. The average dose to pharyngeal constrictor muscles (PCM) at the time of reRT showed an association with the risk of grade ≥ 2 dysphagia: AUC = 0.78 (95% CI: 0.53-1), optimal cut-off value = 36.7 Gy (sensitivity 62%/specificity 100%). The average dose to the oral cavity at the time of reRT showed an association with the risk of grade ≥ 2 dysgeusia: AUC = 0.96 (0.89-1), optimal cut-off value = 20.5 Gy (sensitivity 100%/specificity 88%). CONCLUSION: Our analysis depicted an association between the dose to OAR and the risk of developing moderate to severe dysphagia and dysgeusia and proposed new dose constraints for PCM (36.7 Gy) and oral cavity (20.5 Gy).

Curative high-dose reirradiation for patients with recurrent head and neck squamous cell carcinoma using IMRT or proton therapy: Outcomes and analysis of patterns of failure.

PURPOSE: To analyze outcomes of patients treated with curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS: Among the 55 patients reirradiated for head and neck cancer from 30/08/2012 to 08/04/2019, 23 had HNSCC and received IMRT (52.2%) or PT (47.8%) at a median maximum dose to the CTV of 66 Gy. RESULTS: After a median follow-up of 41.3 months, 18 patients developed a locoregional recurrence (LR), of which eight (44.4%) occurred within the previously reirradiated volume. Two-year locoregional failure-free survival and overall survival were 18.3%[95%CI:7.1%-47.1%] and 42.5%[95%CI:26.2%-69.1%], respectively. Disease-free survival was significantly longer in the PT group (p = 0.031). Main late grade ≥2 toxicities were dysphagia and trismus. CONCLUSION: Curative reRT in HNSCC is possible for selected cases, but the LR rate in the irradiated field and the risk of toxicity grade ≥2 remain high.

High-dose proton therapy and tomotherapy for the treatment of sacral chordoma: a retrospective monocentric study.

OBJECTIVE: Radiation therapy (RT) is used for the treatment of sacral chordoma, in combination with surgery or alone for unresected tumours, to improve local control (LC) and potentially overall survival (OS). The purpose of the present study was to evaluate efficacy and toxicity of proton therapy (PT), and/or intensity modulated radiation therapy (IMRT), particularly Tomotherapy, for sacral chordoma treatment. Material: Between November 2005 and June 2018, 41 consecutive patients who were not included in clinical trials, received sacral chordoma radiation treatment in Institut Curie with Tomotherapy alone in 13 patients, and combined PT and Tomotherapy boost (Proton - Tomo) in 28 patients. RT was delivered as the exclusive local treatment in 11 patients, and as a post-operative complementary treatment in 30 patients. RESULTS: After a median follow-up of 46 months (range, 0-125 months), eight local relapses were observed, and seven patients developed distant metastasis (particularly bone and lung). The 2- and 5- year local relapse rates were 11.4% CI (0.65-22.2%) and 29% (10.5-47.4%), respectively. Over the follow-up period, ten patients died (24.4%). The estimated 2- and 5-year OS rates were 91.4% CI (82.5-100%) and 74.5% (59.4-93.5%), respectively. Fibrosis, cauda equina syndrome, and pain were the most common late toxicities. The comparison between Tomotherapy alone and Proton - Tomo revealed that acute and late cystitis were significantly more frequent in the Tomotherapy group: SHR = 0.12 IC95% (0.01-0.90 [p = .04]), as well as late proctitis. A dosimetric comparison confirmed the interest of PT to spare rectum and bladder in this context. CONCLUSION: RT remains essential to improve local control in sacral chordoma. The combination of proton and photon seems to improve organ at risk sparing, resulting in a decreased rate of reported late toxicities.

The use of new delineation tool "MIRADA" at the level of regional lymph nodes, step-by-step development and first results for early-stage breast cancer patients.

OBJECTIVE:: To describe the practical procedure of implementation and optimization of delineation using "Mirada" software, as well as evaluation of the automatic segmentation for the daily practice of lymph nodes (LN) and organs at risk (OARs) in early stage breast cancer patients. METHODS:: 40 patients' CT scans in treatment position were selected and recontoured according to the European Society of Therapeutic Radiation Oncology guidelines. The atlas of data set was then created for automatic delineation. 30 patients with breast/chest wall and lymph nodes regions irradiated were recruited for evaluation. With the same treatment position, the CT scan images were acquired and then contoured by the MIRADA system automatically as well as by the radiation oncologist manually (as the reference). The conformity index (CI) was used to evaluate the concordance between both of them. RESULTS:: The mean time for manual contour was 24.1 ± 5.1 and 26.4 ± 2.8 min for the LN and the OARs respectively. All the volumes of interest were contoured using the software (including corrections) in 30 min, which reduced the time of delineation of target volumes and OAR by about 40%. Of the 30 cases evaluated, the mean CI of 5 principal OARs showed ≥0.8. While the automatic contour of LN was less satisfactory with mean CI of 0.43 ± 0.1 (0.23-0.52). CONCLUSION:: For the breast cancer patients, the studied software permitted to save time for delineation with acceptable OAR contours. The improvement of LN regions contour is needed. More cases and further evaluation are needed for the system to realize its routine use. ADVANCES IN KNOWLEDGE:: It's the first description and evaluation of the automatic delineation and segmentation system for the breast cancer.

Pelvic insufficiency fracture (PIF) incidence in patients treated with intensity-modulated radiation therapy (IMRT) for gynaecological or anal cancer: single-institution experience and review of the literature.

OBJECTIVE: To summarize the results of pelvic insufficiency fracture (PIF) incidence in patients with anal or gynaecological cancer treated by pelvic intensity-modulated radiation therapy (IMRT). METHODS: The clinical and morphological (CT and/or pelvic MRI) characteristics of patients treated by IMRT at our institution between 2007 and 2014 were analyzed. The global incidence of PIF after external beam radiotherapy and the impact of tumour site (gynaecological or anal cancer) were determined. A dosimetric study was then performed to compare patients with and without pelvic fracture. RESULTS: 341 patients were treated by IMRT for gynaecological or anal cancer between 2007 and 2014. 15 patients experienced at least 1 pelvic fracture after external beam radiotherapy, corresponding to an overall incidence of 4.4%. Age and menopausal status were correlated with an increased fracture risk (p = 0.0274 and p < 0.0001, respectively). The site of the primary tumour (gynaecological or anal canal) was not associated with an excess fracture risk. The median maximum dose received at the fracture site was 50.3 Gy (range: 40.8-68.4 Gy). CONCLUSION: The incidence of pelvic fracture after IMRT is low, but is higher after the age of 50 and in patients who are postmenopausal. Pre-treatment evaluation of bone density by bone densitometry and phosphorus-calcium assessment could be useful prior to the management of these patients. Advances in knowledge: Pelvic fractures are a frequent complication after radiotherapy. The influence of IMRT and clinical characteristics were evaluated in this study.

Helical tomotherapy for inoperable breast cancer: a new promising tool.

BACKGROUND: We investigated the feasibility of helical tomotherapy (HT) for inoperable large breast tumors, after failing to achieve adequate treatment planning with conformal radiation techniques. MATERIAL AND METHODS: Five consecutive patients with locally advanced breast cancer (LABC) were treated by preoperative HT. All patients received up-front chemotherapy before HT. Irradiated volumes included breast and nodal areas (45-50 Gy) in 4 patients. One patient received a simultaneous integrated boost (55 Gy) to gross tumor volume (GTV) without lymph node irradiation. Acute toxicity was assessed with Common Toxicity Criteria for Adverse Events v.4. Patients were evaluated for surgery at the end of treatment. RESULTS: Patients were staged IIB to IIIC (according to the AJCC staging system 2010). HT was associated in 4 patients with concomitant chemotherapy (5-fluorouracil and vinorelbine). Two patients were scored with grade 3 skin toxicity (had not completed HT) and one with grade 3 febrile neutropenia. One patient stopped HT with grade 2 skin toxicity. All patients were able to undergo mastectomy at a median interval of 43 days (31-52) from HT. Pathological partial response was seen in all patients. CONCLUSIONS: HT is feasible with acceptable toxicity profiles, potentially increased by chemotherapy. These preliminary results prompt us to consider a phase II study.

Further developments for improving response and tolerance to irradiation for advanced renal cancer: concurrent (mTOR) inhibitor RAD001 and helical tomotherapy.

PURPOSE: Radiotherapy remains marginal in the treatment of renal cell carcinoma (RCC), due to radioresistance and risks of acute toxicity. However, recent data have shown that the m-TOR inhibitors could decrease the tumor resistance to ionizing radiation. At the same time, new highly conformal irradiation modalities may significantly improve the tolerance to radiation. METHODS: Here, we report the first case of concurrent use of mTOR antagonist, rapamycin and Helical Tomotherapy and its potential in critical organs sparing in a patient with retroperitoneal relapse from a RCC. He was treated with Everolimus, 10 mg/d and concurrent Helical Tomotherapy to the region of the recurrence (45 Gy, 1.8 Gy per fraction). RESULTS: Helical Tomotherapy allowed very sharp dose distributions around the target volumes, while sparing critical organs from useless radiation. No radiotherapy related acute toxicity was observed. At last follow-up (6 months later), the patient remains in partial remission at the irradiated region. CONCLUSIONS: While targeted agents might find applications for radiosensitizing purposes, this report highlights the potential of Helical Tomotherapy for reducing the doses delivered to the critical organs, thus improving tolerance to irradiation.

Solitary plasmocytoma: improvement in critical organs sparing by means of helical tomotherapy.

PURPOSE: Helical tomotherapy (HT) was assessed in two patients with paramedullar solitary bone plasmocytoma. We compared doses delivered to critical organs, according HT plan or tridimensional conformal plan. METHODS AND MATERIALS: One male (patient no. 1), 67 yr-old and one female (patient no. 2), 37-yr-old, with histologically, biologically and radiological confirmed paramedullar solitary plasmocytoma have been treated in our department between November 2007 and February 2008 using HT. The prescription dose was 40 Gy in 20 fractions. This HT treatment planning was compared with a routine dosimetric work that was executed for a standard conformal radiotherapy treatment planning. RESULTS: Treatment tolerance was excellent, without any side effects. Both patients achieved 9-month complete remission. HT resulted in substantial critical organs sparing. For patient no. 1, dose delivered to 20% of the total intestine volume was reduced from 28 Gy for conformal radiotherapy to 13 Gy for HT. Radiation dose delivered to 20% of the left kidney was reduced from 25 Gy to 7 Gy. For patient no. 2, volume of left lung that received at least 20 Gy was 12% for conformal radiotherapy vs. 6% for HT. CONCLUSIONS: For paramedullar solitary plasmocytoma, HT has the potential to significantly improve the quality of the dose distribution both in terms of better dose homogeneity within the planning target volume and more efficient sparing of critical organs.