Search

Triple-negative breast cancer (TNBC) cells are sensitive to PARP1 inhibitors in vitro. The combination of Olaparib and radiotherapy for TNBC is currently evaluated in the Phase I RADIOPARP trial. RADIOPARP is a monocentric prospective open-label Phase I dose-escalation trial evaluating the combination of breast radiotherapy and Olaparib in TNBC patients with inflammatory, locoregionally advanced or metastatic disease, or with residual disease after neoadjuvant chemotherapy. Olaparib was orally given at increasing dose levels (50, 100, 150 or 200 mg twice a day [BID]); radiotherapy consisted of 50 Gy to the breast or chest wall with or without lymph node irradiation. Twenty-four TNBC patients were enrolled between September 2017 and November 2019. Olaparib was escalated to 200 mg BID without dose-limiting toxicities. At 1-year follow-up, no treatment-related grade ≥3 toxicity was observed. One patient (4.2%) had persistent grade 2 adverse events (breast pain, fibrosis and deformity). There was no cardiac, pulmonary or digestive toxicity related to treatment. The 1-year follow-up report of the RADIOPARP Phase I trial, evaluating Olaparib associated with breast radiotherapy in TNBC patients, consequently demonstrated an excellent toxicity profile of this combination with few low-grade adverse events., (© 2021 UICC.)

Objectives: To retrospectively report the clinical and therapeutic features of children with nasopharyngeal carcinoma (NPC) treated by chemotherapy and doses adapted of radiotherapy., Patients and Methods: From 1978 to 2005, 34 children were treated for NPC. All histologic and/or cytologic samples and CT scans were reviewed. Cervical nodal irradiation was reduced (<50 Gy) in the case of a good response to chemotherapy (>/=90% of initial tumor volume)., Results: Thirty-two children had metastatic cervical nodes and one child had systemic metastases at diagnosis. All children had AJJC-TNM Stage IV. Thirty-one children received neoadjuvant chemotherapy with various regimens. The overall chemotherapy response rate was 78%. Fifteen patients had cervical nodal irradiation dose reduced: Median 47 Gy (range: 45-50). Nasopharyngeal radiotherapy was delivered at a dose of 59.4 Gy (range: 45-66). Local and distant failure rates were 10% and 18%, respectively. The 5-year overall survival was 73 +/- 8% and the event-free survival (EFS) was 75 +/- 8%., Conclusions: The overall prognosis was not influenced by TNM status, dose of local radiotherapy delivered or response to initial chemotherapy, but EFS was better in patients with a good response to chemotherapy. The cervical local failure rate was low despite radiotherapy dose reduction in the case of a good response to neoadjuvant chemotherapy. We also propose a reduction of nasopharyngeal radiation (

Objective: To assess the visualisation of the left anterior descending (LAD) coronary artery on CT images used for breast radiation treatment planning. Methods: Delineation of the LAD artery was achieved for 25 breast patients by 1 radiologist and 1 radiation oncologist independently on two sets of images for each patient: one pre-operative CT scan using intravenous (IV) contrast media to determine the primary gross tumour volume (GTV) and one post-operative CT scan used for treatment planning. A Student's paired t-test was used to compare the number of CT slices in which the LAD was visible for each patient in the two series. Interpolations and extrapolations of the LAD volume were performed for the left-sided cases using a published heart atlas in order to report doses to the LAD structure. Results: There was a non-significant difference between the results with and without IV contrast media (p=0.34 for the radiologist; p=0.90 for the radiation oncologist). The visible LAD artery corresponded to a 30% portion (range 12-47%) of the interpolated structure. The maximum dose to the left artery varied widely, from 2.7 to 41.7Gy, in the group of patients with left breast tumours. The largest values (>25Gy) corresponded to those patients in whom the LAD artery distal extremity lay inside the breast fields. Conclusions: With the current planning CT protocol, only one-third of the LAD artery could be objectively visualised. Contrast-enhanced imaging used for GTV delineation before the breast surgery did not improve the visualisation of the artery. Advances in Knowledge: This study has revealed the lack of consistency that may be encountered when contouring heart vessels, thereby questioning the reliability of dose reporting. [ABSTRACT FROM AUTHOR]

This study is an analysis of the criteria considered when prescribing concomitant chemotherapy and radiotherapy, as a routine treatment for patients with anal canal cancer, and related complications. Between 1990 and 1996, 67 patients were treated at Institut Curie for invasive, nonmetastatic cancer of the anal canal. Median age was 65 years (range, 35-90 years). TNM stage distribution was as follows: seven T1, 17 T2, 27 T3, 16 T4, and 22 N+ patients. A total of 29 patients (i.e., five T1/T2, and 24 T3/T4) received concurrent chemotherapy and radiotherapy. Radiotherapy volumes and dose and prescribed dose for chemotherapy were not statistically different from one group of patients to another. Only 55% of T3/T4 patients underwent standard chemoradiation treatment for anal canal cancer. Age was the one of main factor in determining if the patient would undergo concomitant chemotherapy or not. For the T3/T4 patients, concomitant chemotherapy was prescribed to 69% of patients <55 years, 90% of patients between 56 and 64 years, 45% of patients between 65 and 75 years, and 20% of patients over 75 years (P<0.02).Overall survival at 4 years was 66%. The 4 years overall survival rate of T3/T4 patients, who underwent concomitant chemotherapy, was 72%, and that of T3/T4 patient who did not, was 34% (P<0.04). The patients who did not undergo chemotherapy were significantly older. The difference in cause-specific survival rates (72 vs 48%) was not significant. Relapse-free interval without local recurrence at 4 years was 70%. Relapse-free interval of T3/T4 patients was 78% with chemotherapy and 60% without chemotherapy (p=NS). Rates of treatment discontinuation and early toxicity were not statistically different. Late complications occurred in 33 patients, eight of whom had grade 2/3 tumours. At 2 years, complications occurred in 39% of patients who had undergone concomitant chemotherapy, and in 20% of patients who had not (p<0.02). Differences in grade 2/3 complications were not significant. In conclusion, although radiotherapy with concomitant chemotherapy is considered the current ‘gold-standard’ treatment for anal canal cancer, in our daily experience, only 55% of our T3/T4 patients have undergone this treatment. The remainder did not undergo chemotherapy mainly because they were deemed too old. In this series, no increase in local control and cause-specific survival was observed in patients who received concomitant chemotherapy; this may be due to the small number of patients included in the series. The increased rate of late complications observed in patients who received the combined treatment, however, provides evidence that this treatment should be restricted to younger patients without comorbidity and therefore justifies our position. Perhaps reduction of doses of chemotherapy must be discussed for older patients.British Journal of Cancer (2003) 89, 2057-2061. doi:10.1038/sj.bjc.6601378 www.bjcancer.com [ABSTRACT FROM AUTHOR]

In order to assess the role of genetic predispositionin the induction of radiation-induced tumors, we performed statistical analysis on data from the literature and from our own Institute with regard to theage at onset and the latency period of osteosarcoma as the second primarytumor for retinoblastoma with or without subsequent radiotherapy. In retinoblastomasurvivors who subsequently developed osteosarcoma, the age at onset of retinoblastomawas young (average of 12 months) in both unilateral and bilateral forms. Thissuggests that all or almost all of the patients were genetically predisposedby a mutation of one allele of the RB1 gene. For retinoblastoma patients, osteosarcomas occurred 1.2 years earlier inside than outside the radiationfield. The latency period between radiotherapy and osteosarcoma onset was1.3 years shorter inside than outside the radiation field. Interestingly,a bimodal distribution of latency periods was observed for osteosarcomasarising inside, but not outside the radiation field: 40% occurred after ashort latency, while the latency of the remaining 60% was comparable to thatof osteosarcoma occurring outside the radiation field. This suggests thatdifferent mechanisms may be involved in radiocarcinogenesis. A radiation-inducedmutation of the second RB1 allele may be the cause of osteosarcomas occurring after a short delay, while other genes may be affected in those occurringafter a longer delay. [ABSTRACT FROM AUTHOR]

Purpose Due to the extensive initial distant tumour spread in metastatic rhabdomyosarcoma, the importance of local treatment is sometimes underestimated. A retrospective study was conducted to identify the prognostic value of aggressive local treatment in paediatric metastatic rhabdomyosarcoma. Patients Patients with metastatic rhabdomyosarcoma aged 1–21 years treated in France from 1998 to 2011 according to European protocols MMT-4-89, 4-91, 98 and recent national guidelines were selected. Survival comparison were performed between patients with ‘aggressive local treatment’ (surgery and radiotherapy) and exclusive surgery or radiotherapy, after exclusion of patients with early progression. End-points were event-free and overall survival (OS). Results A total of 101 children, median age 9 years, with majority of primaries in unfavourable sites (73 patients, pts), T2 tumours (66 pts), alveolar subtypes (65 pts) and large tumours (>5 cm, 83 pts) received various chemotherapy regimens. On univariate and multivariate analyses, OS was better after ‘aggressive local treatment’ (49 pts; 44.3 ± 8%), than after exclusive surgery (10 pts; 18.8% ± 15.5%) or exclusive radiotherapy (29 pts; 16.1 ± 7.2%, P < 0.006). Moreover, OS was better in the case of surgery with complete resection (41.1 ± 10.2%) or microscopic residue (56.4 ± 14.9%) than macroscopic residue (20.0 ± 12.6%; P < 0.03). Conclusions In this large retrospective analysis, OS appeared to be better for patients receiving ‘aggressive local treatment’ even after adjustment for the initial patient and tumour characteristics. Isolated debulking surgery is associated with a very poor outcome and should be avoided. Aggressive local treatment in patients with rhabdomyosarcoma, even with metastasis, should be seriously considered. [ABSTRACT FROM AUTHOR]

Preclinical studies have demonstrated that triple-negative breast cancer (TNBC) cells are sensitive to PARP inhibitors when used as radiosensitizers. Combining PARP-inhibitors with radiotherapy in TNBC patients may consequently enhance the biological effectiveness of the irradiation ultimately leading to improved locoregional control. We aimed to establish the appropriate dosing and safety profile of Olaparib used as a radiosensitizer in combination with radiotherapy in TNBC patients with residual disease after neoadjuvant chemotherapy. RADIOPARP (NCT03109080) was a prospective phase I dose-escalation trial establishing the tolerance profile of Olaparib combined with breast radiotherapy in high-risk early TNBC patients. Inclusion criteria were resected TNBC with non-complete pathological response after neoadjuvant chemotherapy, or unresectable TNBC despite prior neoadjuvant chemotherapy. Olaparib was started seven days before irradiation and continued during radiotherapy. A time-to-event continual reassessment method was used to increase Olaparib through four increasing dose levels (50mg, 100mg, 150mg or 200mg twice a day) with a 25% maximum probability rate of dose-limiting toxicities (DLT). Radiotherapy delivered 50 Gy to the breast or the chest wall, with or without lymph node irradiation. Toxicities were graded according to CTCAE (version 4.03). Homologous recombination (HR) proficiency status was genetically determined based on shallow whole genome sequencing. Twenty-four TNBC patients were enrolled between 09/2017 and 11/2019. Olaparib was escalated to 200 mg twice a day without DLT and the MTD was not reached. With a median follow-up of 34 months, no late treatment-related grade ≥ 3 toxicity was observed, and the maximum observed treatment-related toxicities were limited to grade 2 breast pain (n=2), fibrosis (n=2), deformity (n=1) and telangiectasia (n=1). Three-year OS and EFS were 83% [95% CI: 70%-100%] and 68% [51%-91%], respectively. HR proficiency status was not associated with OS and EFS. Olaparib used as a radiosensitizer in combination with breast radiotherapy in TNBC patients was well-tolerated. The MTD was not reached, and no significant late toxicity was reported. For future trials evaluating the anti-tumor efficacy of this combination, an Olaparib dose of 200 mg twice a day should be considered. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Preclinical studies have found that triple-negative breast cancer (TNBC) cells were sensitive to PARP1 inhibitors. The phase I dose-escalation RADIOPARP trial evaluated in TNBC patients the combination of breast radiotherapy and Olaparib, which was escalated to the target dose of 200 mg twice a day without dose-limiting toxicities. We report the one-year toxicity of this trial.Materials/methods: RADIOPARP is a monocentric prospective open-label phase I dose escalation trial evaluating the combination of breast radiotherapy and Olaparib in TNBC patients with inflammatory, locoregionally advanced or metastatic disease, or with residual disease after neoadjuvant chemotherapy. Olaparib was orally given at increasing dose levels (50mg, 100mg, 150mg or 200mg twice a day); radiotherapy consisted of 50 Gy to the breast or chest wall with or without lymph node irradiation. One-year treatment-related toxicity was graded according to the CTCAE (version 4.03).Results: Twenty-four TNBC patients were enrolled between 09/2017 and 11/2019. Olaparib was escalated to 200 mg twice a day without dose-limiting toxicities. At one-year follow-up, no treatment-related grade ≥3 toxicity was observed (Table 1). Three patients had persistent grade 2 adverse events (breast pain, fibrosis and deformity); there were no cardiac, pulmonary or digestive toxicity.Conclusion: The one-year follow-up of the RADIOPARP phase I trial, evaluating breast radiotherapy with Olaparib in TNBC patients, demonstrated an acceptable toxicity profile of this combination with few low-grade adverse events. [ABSTRACT FROM AUTHOR]

Childhood malignant brain stem tumours have a very poor prognosis with a median survival of 9 months despite radiotherapy. No chemotherapy has improved survival. However, carboplatin has been reported to have activity in glial tumours as well as antitumour synergy with radiation. Our aims were to test the response rate of these tumours to carboplatin alone and to evaluate the efficacy on survival of carboplatin alone followed by concurrent carboplatin and radiotherapy. Patients younger than 16 years with typical clinical and radiological presentation of infiltrating brain stem tumour, as well as histologically-documented cases in the atypical forms, were eligible. Two courses of carboplatin (1050 mg/m2 over 3 days) were administered initially. This treatment was followed by a chemoradiotherapy phase including five weekly carboplatin courses (200 mg/m2) and conventional radiotherapy. 38 eligible patients were included. No tumour response was observed after the initial phase. This schedule of first-line carboplatin followed by concurrent carboplatin and radiotherapy did not improve survival. [Copyright &y& Elsevier]