Transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma: Long-term results of RTF3 regimen

PurposeIn early-stage hepatocellular carcinoma (HCC) patients merely fit for surgery, transarterial chemoembolization (TACE) achieve low long-term disease control. We evaluated the efficacy and safety of its combination with moderately hypofractionated radiotherapy (hRT) using RTF3 regimen.Material and methodsBetween 2006 and 2016, 61 consecutive patients treated in our single expert center for a Barcelona Clinic Liver Cancer (BCLC) A HCC by TACE followed by hRT 3 Gy/fraction were retrospectively included.ResultsSixty of the 61 included presented Child-Pugh A cirrhosis (A5, n = 41, 67.2%; A6: n = 19, 31.1%). Fourteen patients (22.9%) were already treated for a HCC, mainly by radiofrequency (n = 12). All patient received a TACE followed by 3 Gy per fraction hRT. Mean radiation dose was 54 Gy (range: 48–60). After a median follow-up of 118 months, median time-to-progression, progression-free survival (PFS) and overall survival (OS) was 21.3, 18.1, and 31.5 months, respectively. In univariate analysis, PFS was related to dose > 54 Gy (HR: 2, P = 0.036), and OS was correlated to Child-Pugh A6 or B7 (HR: 1.93, P = 0.03) and overall hRT time (HR: 1.06, P = 0.015). At progression, orthotopic liver transplantation was performed in 8 patients (13.1%). Severe symptomatic adverse events occurred in 12 patients (19.7%), mainly ascites (n = 7).ConclusionIn BCLC-A Child-Pugh A HCC patients ineligible to surgery or thermoablation, TACE-hRT is a safe and effective treatment. Prospective studies are needed to compare this association with radioembolization, TACE-stereotactic radiotherapy, and systemic treatments combinations.     

Effective local control of advanced soft tissue sarcoma with neoadjuvant chemoradiotherapy and surgery: A single institutional experience

PurposeThere is a sound theoretical basis but little clinical evidence substantiating the benefits of concurrent chemoradiotherapy with two-drug chemotherapy for locally advanced soft tissue sarcomas. Our five-year data on the feasibility and effectiveness of neoadjuvant chemoradiotherapy with systemically effective doses of adriamycin and ifosfamide combined is presented here.Patients and methodsBetween 2000 and 2011, 53 patients with UICC (2010) stage I (n = 1, 1.9%), II (n = 12, 22.7%) or III (n = 40, 75.5%) nonmetastatic soft tissue sarcoma received neoadjuvant chemoradiotherapy with ifosfamide (1.5 g/m²/day, d1–5, q28) and doxorubicin (50 mg/m²/day, d3, q28) plus concurrent radiotherapy with a target dose of 50–64 Gy (median 60 Gy). The treatment of 34 patients (64.2%) was combined with hyperthermia.ResultsAt five years, the local control rate was 89.9% (± 5.7%), distant metastasis-free survival 66.6% (± 7.6%), and survival 83.3% (± 6%). The R0 resection rate was 81.1%. Radiotherapy was completed as planned in all patients and chemotherapy in 42/53 (70.2%). Grades III (n = 21, 29.6%) and IV (n = 18, 34%) leukopenia was the main acute adverse event. All acute and chronic non-hematologic toxicities were moderate.ConclusionNeoadjuvant chemoradiotherapy for soft tissue sarcoma is associated with good feasibility, manageable acute and late toxicities, and high local efficacy.     

Intraoperative partial irradiation for highly selected patients with breast cancer: Results of the INTRAOBS prospective study

PurposeTo evaluate our long-term experience on one-day breast intraoperative radiotherapy (IORT) given as sole radiation treatment to selected patients with breast cancer.Methods and materialsInclusion criteria of INTRAOBS study (prospective observational study) were: ER+ T1N0 unifocal ductal carcinoma; absence of lymphovascular invasion or of extensive intraductal component (Scarff-Bloom-Richardson grade III and HER2+++ excluded). Two different linacs were used (20 Gy/1 fraction): one dedicated electron linac (< October 2011), and afterwards a mobile linac (50 kV photons). The primary endpoint was the local recurrence rate (=ipsilateral breast cancer recurrences number). Secondary endpoints were recurrence-free survival (RFS), overall and specific survival, cosmetic results, and patient satisfaction.ResultsOf the present pre-planned analysis for the first 200 patients (median age: 68 years; range, 59–87 years) who received IORT between January 2010 and October 2014 (median follow-up of 53.4 months). A total of 193 patients were still alive. The local recurrence rate was 2.5% (n = 5). The 1- and 5-year local RFS rates were 100% and 95.2%, respectively. At 12 months post-surgery, satisfaction about IORT was excellent for 86.9% of patients. Cosmetic results were considered by patients and physicians as good or very good in 89.4% and 97.3% of cases, respectively.ConclusionsIORT for selected patients with breast cancer shows low recurrence rates, good cosmetic outcomes and excellent satisfaction.     

Stereotactic radiotherapy for large solitary brain metastases

PurposeTo assess effectiveness and toxicity levels of stereotactic radiation therapy without whole brain radiation therapy in patients with solitary brain metastases larger than 3 cm.Patients and methodsBetween June 2007 and March 2009, 12 patients received fractionated stereotactic radiation therapy and 24 patients underwent stereotactic radiosurgery. For the fractionated stereotactic radiation therapy group, 3 × 7.7 Gy were delivered to the planning target volume (PTV); median volume and diameter were 29.4 cm³ and 4.4 cm, respectively. For the stereotactic radiosurgery group, 14 Gy were delivered to the PTV; median volume and diameter were 15.6 cm³ and 3.7 cm, respectively.ResultsMedian follow-up was 218 days. For the fractionated stereotactic radiation therapy group, local control rates were 100% at 360 days and 64% at 720 days; for the stereotactic radiosurgery group, rates were 58% at 360 days and 48% at 720 days (P = 0.06). Median survival time was 504 days for the fractionated stereotactic radiation therapy group and 164 days for the stereotactic radiosurgery group (P = 0.049). Two cases of grade 2 toxicity were observed in the fractionated stereotactic radiation therapy group, and 6 cases of grade 1–2 toxicity, in the stereotactic radiosurgery group.ConclusionsThis study provides data to support that fractionated stereotactic radiation therapy without whole brain radiation therapy with a margin dose of 3 fractions of 7.7 Gy for treatment of solitary large brain metastases is efficient and well-tolerated. Because of the significant improvement in overall survival, this schedule should be assessed in a randomized trial.     

Tolérance et efficacité de la radiothérapie préopératoire chez les patients âgés atteints d’un cancer du rectum

PurposeTo retrospectively assess the impact of age on tolerance and oncologic outcomes treated by neoadjuvant treatment for patients of 70 years old or above with locally advanced rectal cancer.Patients and methodsNinety-one consecutive patients were divided into three groups: group 1 from 70 to 75 years (n = 31); group 2: 76 to 79 years (n = 31) and group 3, patients aged 80 years or above (n = 29). Radiation therapy was delivered according two schemes: 25 Gy in five fractions (short scheme) or 45 to 50 Gy with a classical fractionation (long scheme). Long scheme patients received a concomitant chemotherapy with 5-fluoro-uracile alone or associated with oxaliplatin.ResultsThe three groups were comparable for performance status, Charlson's score and T staging. Long scheme radiation therapy and chemotherapy were performed in 77.5, 74.5 and 48.3% of patients (P = 0.03) and 77.4, 71 and 41.4% (P = 0.006) in the groups 1, 2 and 3, respectively. All patients treated with the short scheme irradiation received the treatment without any acute toxicity. In the long scheme group, 65% of patients received the treatment on time and grade 3 or above toxicity was observed in 12% of patients who did not receive oxaliplatin and in 48% of patients who received oxaliplatin. The overall survival rate at 3 and 5 years was 66.9% and 60.8% in the group 1, 90.5% and 75.9% in the group 2 and 80.5% and 73.8% in the group 3 (P = 0.15).ConclusionNeoadjuvant treatment is feasible with encouraging survival rates for patients aged 70 years and older. Short scheme radiation therapy seems to be an interesting option in this population.     

Radiomics: A primer for the radiation oncologist

PurposeRadiomics are a set of methods used to leverage medical imaging and extract quantitative features that can characterize a patient's phenotype. All modalities can be used with several different software packages. Specific informatics methods can then be used to create meaningful predictive models. In this review, we will explain the major steps of a radiomics analysis pipeline and then present the studies published in the context of radiation therapy.MethodsA literature review was performed on Medline using the search engine PubMed. The search strategy included the search terms “radiotherapy”, “radiation oncology” and “radiomics”. The search was conducted in July 2019 and reference lists of selected articles were hand searched for relevance to this review.ResultsA typical radiomics workflow always includes five steps: imaging and segmenting, data curation and preparation, feature extraction, exploration and selection and finally modeling. In radiation oncology, radiomics studies have been published to explore different clinical outcome in lung (n = 5), head and neck (n = 5), esophageal (n = 3), rectal (n = 3), pancreatic (n = 2) cancer and brain metastases (n = 2). The quality of these retrospective studies is heterogeneous and their results have not been translated to the clinic.ConclusionRadiomics has a great potential to predict clinical outcome and better personalize treatment. But the field is still young and constantly evolving. Improvement in bias reduction techniques and multicenter studies will hopefully allow more robust and generalizable models.     

Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: Multicentre,open-label,phase II safety study

PurposeWe assessed the safety of the multikinase inhibitor regorafenib in patients with hepatocellular carcinoma (HCC) that had progressed following first-line sorafenib.Patients and methodsThirty-six patients with Barcelona Clinic Liver Cancer stage B or C HCC and preserved to mildly impaired liver function (Child–Pugh class A) received regorafenib 160 mg once daily in cycles of 3 weeks on/1 week off treatment until disease progression, unacceptable toxicity, death or patient/physician decision to discontinue. The primary end-point was safety; secondary end-points included efficacy (including time to progression and overall survival).ResultsThe median treatment duration was 19.5 weeks (range 2–103). At data cutoff, three patients remained on treatment. Reasons for discontinuation were adverse events (n = 20), disease progression (n = 10), consent withdrawal (n = 2) and death (n = 1). Seventeen patients required dose reductions (mostly for adverse events [n = 15]); 35 patients had treatment interruption (mostly for adverse events [n = 32] or patient error [n = 11]). The most frequent treatment-related adverse events were hand–foot skin reaction (any grade n = 19; grade ?3 n = 5), diarrhoea (n = 19; n = 2), fatigue (n = 19; n = 6), hypothyroidism (n = 15; n = 0), anorexia (n = 13; n = 0), hypertension (n = 13; n = 1), nausea (n = 12; n = 0) and voice changes (n = 10; n = 0). Disease control was achieved in 26 patients (partial response n = 1; stable disease n = 25). Median time to progression was 4.3 months. Median overall survival was 13.8 months.ConclusionRegorafenib had acceptable tolerability and evidence of antitumour activity in patients with intermediate or advanced HCC that progressed following first-line sorafenib.     

Efficacy and safety of S-1 (tegafur,gimeracil, and oteracil potassium) concurrent with 3-dimensional conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients

PurposeThis study evaluated the efficacy and safety of the combination drug tegafur, gimeracil, and oteracil potassium (S-1) concurrent with 3-dimensional conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients.Patients and methodsPatients with pathologically or cytologically newly diagnosed lung squamous cell carcinoma (n = 106) were randomly assigned to receive the combination of tegafur, gimeracil, and oteracil potassium (40 mg/m², BID, d1−28, repeated every 6 weeks for 4 cycles) and concurrent 3D-conformal radiotherapy (60 Gy; experimental group), or gemcitabine (800−1000 mg/m², d1 and d8) repeated every 21 days for 4 cycles as well as 3D-conformal radiotherapy (control group).ResultsThe overall response rate (complete and partial responses) of the experimental group was 68.6%, which was significantly higher than that of the control group (38.5%; P = 0.002). The median progression-free survival rates of the experimental and control groups were 11.8 months (95% confidence interval [CI]: 8.0 − 22.4) and 7.8 months (95% CI, 6.9–9.2), respectively (P = 0.017). Adverse reactions included grade I/II radiation esophagitis and pneumonitis, with good tolerance. Grade III/IV adverse reactions of the experimental and control groups were leucopenia (20% cf. 56.6%, respectively; P = 0.027), thrombocytopenia (3.9% cf. 25%; P = 0.037), and gastrointestinal reaction (1.9% cf. 3.5%; P = 0.35).ConclusionThe efficacy of concurrent combination chemotherapy with tegafur, gimeracil, and oteracil potassium (S-1) and 3D-conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients was excellent, and all toxicities were well tolerated. This treatment might be considered a main regimen in the management of squamous cell carcinoma of the lung in elderly patients.     

Comparison of dosimetric parameters and acute toxicity of intensity-modulated and three-dimensional radiotherapy in patients with cervix carcinoma: A randomized prospective study

PurposeThe use of intensity-modulated radiotherapy (IMRT) to treat cervix carcinoma has increased, however prospective randomized trials are still lacking.AimTo compare the dosimetric parameters and associated acute toxicity in patients with cervix carcinoma treated with three-dimensional (3D) conformal radiotherapy and IMRT.Patients and methodsForty patients were randomized in two arms each consisting of 20 patients. Patients in both arms received concurrent chemoradiation (cisplatin 40 mg/m² weekly; 50 Gy/25 fractions). Patients were treated with 3D conformal radiotherapy in one arm and with IMRT in another arm. After external beam radiotherapy, all patients received brachytherapy (21 Gy/3 fractions at weekly interval). For dosimetric comparison, both kinds of the plans were done for all the patients. All patients were assessed throughout and until 90 days after completion of treatment for acute gastrointestinal, genitourinary and hematologic toxicities.ResultsBoth plans achieved adequate planning target volume coverage, while mean conformity index was found significantly better in IMRT plans (P-value = 0.001). D₃₅ (dose to 35% volume) and D₅₀ for bladder was reduced by 14.62 and 32.57% and for rectum by 23.82 and 43.68% in IMRT. For IMRT, V₄₅ (volume receiving 45 Gy) of bowel were found significantly lesser (P-value = 0.0001), non-tumour integral dose was found significantly higher (P-value = 0.0240) and V₂₀ of bone marrow was found significantly reduced (P-value = 0.019) in comparison to that in 3D conformal radiotherapy. Significant reduction of grade 2 or more (20 vs 45%; P-value = 0.058) and grade ≥ 3 (5 vs 15%, P-value = 0.004) acute genitourinary toxicity and grade 2 or more (20 vs 45%, P-value = 0.003) and grade 3 or more (5 vs. 20%, P-value = 0.004) acute gastrointestinal toxicity while no significant difference for grade 2 and 3 or more haematological toxicity was noted in patients treated with IMRT compared to 3D conformal radiotherapy.ConclusionIMRT provide a good alternative for treatment of cervix carcinoma with lower acute gastrointestinal and acute genitourinary toxicity with similar target coverage compared to 3D conformal radiotherapy.     

Meta-analysis of prophylactic cranial irradiation or not in treatment of extensive-stage small-cell lung cancer: The dilemma remains

PurposeThe role of prophylactic cranial irradiation (PCI) in treatment of extensive-stage small-cell lung cancer (SCLC) is controversial. The aim of this study was to systematically evaluate the efficacy and safety of using PCI in the treatment of extensive-stage SCLC. In the present study, we examined whether PCI was essential for the optimal treatment of extensive-disease small-cell lung cancer.Material and methodsWe searched the PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify articles that assessed the efficacy of PCI in treating extensive-stage small-cell lung cancer patients.ResultsWe identified 8 studies that involved a total of 982 patients who received PCI (PCI group) and a total of 4509 patients who did not receive PCI (control group). The results showed that PCI significantly improved the 1-year overall survival rate (HR = 1.50; 95% CI: 1.23–1.82; I² = 67%; P < 0.0001) and reduced the incidence of brain metastasis (HR = 0.46; 95% CI: 0.37–0.58; I² = 6%; P < 0.00001).ConclusionPCI improves the 1-year overall survival rate and reduces the risk of brain metastasis in patients with extensive-stage SCLC.     

Esthésioneuroblastome : étude rétrospective et revue de la littérature

PurposeOlfactory neuroblastoma or esthesioneuroblastoma is a rare entity among head and neck neoplasms. In this paper, we report the experience of our institution and compare it with a comprehensive review of the literature.Patients and methodsWe retrospectively analysed clinical and treatment data of patients referred to the Lyon Sud University Hospital (France) for histologically proven olfactive esthesioneuroblastoma.ResultsTen patients treated between 1993 and 2015 have been analysed. Disease stage at diagnosis, according to the Kadish staging system, was C in 90% of cases. Median follow-up was 136 months. Ten-year overall survival was 90%. Five- and ten-year progression-free survival were 70% and 50%. Nine patients (90%) underwent surgical resection first. Seven of the nine patients who underwent resection (77%) received adjuvant three-dimensional (3D)-conformal radiotherapy (n = 7), intensity-modulated radiotherapy (n = 1), or volumetric arctherapy (n = 1). The mean dose to the tumour volume was 61 Gy. None of the patients received elective nodal irradiation. Two patients received concurrent chemotherapy. Five patients (50%) presented with disease recurrence, which was local (n = 1), nodal (n = 2) and cerebral (n = 2).ConclusionOur results are consistent with the literature. Because of the lack of prospective study and the low number of cases in the literature, each institution's experience is of the utmost important to improve standardised management of these tumours.     

Prediction of toxicity outcomes following radiotherapy using deep learning-based models: A systematic review

PurposeThis study aims to perform a comprehensive systematic review of deep learning (DL) models in predicting RT-induced toxicity.Materials and methodsA literature review was performed following the PRISMA guidelines. Systematic searches were performed in PubMed, Scopus, Cochrane and Embase databases from the earliest record up to September 2022. Related studies on deep learning models for radiotherapy toxicity prediction were selected based on predefined PICOS criteria.ResultsFourteen studies of radiotherapy-treated patients on different types of cancer [prostate (n = 2), HNC (n = 4), liver (n = 2), lung (n = 4), cervical (n = 1), and oesophagus (n = 1)] were eligible for inclusion in the systematic review. Information regarding patient characteristics and model development was summarized. Several approaches, such as ensemble learning, data augmentation, and transfer learning, that were utilized by selected studies were discussed.ConclusionDeep learning techniques are able to produce a consistent performance for toxicity prediction. Future research using large and diverse datasets and standardization of the study methodologies are required to improve the consistency of the research output.     

Overall survival with cisplatin–gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL)

BackgroundBevacizumab, the anti-vascular endothelial growth factor agent, provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer. We report the final overall survival (OS) analysis from the phase III AVAiL trial.Patients and methodsPatients (n = 1043) received cisplatin 80 mg/m² and gemcitabine 1250 mg/m² for up to six cycles plus bevacizumab 7.5 mg/kg (n = 345), bevacizumab 15 mg/kg (n = 351) or placebo (n = 347) every 3 weeks until progression. Primary end point was progression-free survival (PFS); OS was a secondary end point.ResultsSignificant PFS prolongation with bevacizumab compared with placebo was maintained with longer follow-up {hazard ratio (HR) [95% confidence interval (CI)] 0.75 (0.64–0.87), P = 0.0003 and 0.85 (0.73–1.00), P = 0.0456} for the 7.5 and 15 mg/kg groups, respectively. Median OS was >13 months in all treatment groups; nevertheless, OS was not significantly increased with bevacizumab [HR (95% CI) 0.93 (0.78–1.11), P = 0.420 and 1.03 (0.86–1.23), P = 0.761] for the 7.5 and 15 mg/kg groups, respectively, versus placebo. Most patients (∼62%) received multiple lines of poststudy treatment. Updated safety results are consistent with those previously reported.ConclusionsFinal analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin–gemcitabine. The PFS benefit did not translate into a significant OS benefit, possibly due to high use of efficacious second-line therapies.     

Risk factors analysis and establishment of predictive nomogram of extranodal B-cell lymphoma of mucosal-associated lymphoid tissue

PurposeThe role of radiation therapy in mucosa-associated lymphoid tissue (MALT) lymphoma is poorly defined. The objective of this study was to explore the factors associated with the performance of radiotherapy and to assess its prognostic impact in patients with MALT lymphoma.Patients and methodsPatients with MALT lymphoma diagnosed between 1992 and 2017 were identified in the US Surveillance, Epidemiology, and End Results database (SEER). Factors associated with the delivery of radiotherapy were assessed by chi-square test. Overall survival (OS) and lymphoma-specific survival (LSS) were compared between patients with and without radiotherapy, using Cox proportional hazard regression models, in patients with early stage as well as those with advanced stage.ResultsOf the 10,344 patients identified with a diagnosis of MALT lymphoma, 33.6% had received radiotherapy; this rate was 38.9% for stage I/II patients and 12.0% for stage III/IV patients, respectively. Older patients and those who already received primary surgery or chemotherapy had a significantly lower rate of receiving radiotherapy, regardless of lymphoma stage. After univariate and multivariate analysis, radiotherapy was associated with improved OS and LSS in patients with stage I/II (HR = 0.71 [0.65–0.78]) and (HR = 0.66 [0.59–0.74]), respectively, but not in patients with stage III/IV (HR = 1.01 [0.80–1.26]) and (HR = 0.93 [0.67–1.29]). The nomogram built from the significant prognostic factors associated with overall survival of stage I/II patients had a good concordance (C-index = 0.749 ± 0.002).ConclusionThis cohort study shows that radiotherapy is significantly associated with a better prognosis in patients with early but not advanced MALT lymphoma. Prospective studies are needed to confirm the prognostic impact of radiotherapy in patients with MALT lymphoma.     

Phase I evaluation of cediranib,a selective VEGFR signalling inhibitor,in combination with gefitinib in patients with advanced tumours

AimCediranib is a highly potent inhibitor of vascular endothelial growth factor receptor (VEGFR) signalling. Preclinical and clinical data suggest that inhibition of the VEGFR and epidermal growth factor receptor (EGFR) pathways may be synergistic. Combination treatment with cediranib and gefitinib, an EGFR signalling inhibitor, was evaluated in patients with advanced solid tumours.Patients and methodsNinety patients received treatment in this four-part, open-label study (NCT00502060). The patients received once-daily oral doses of cediranib (20–45 mg) and gefitinib 250 mg (part A1; n = 16) or 500 mg (part B1; n = 44). A cohort expansion phase investigated the potential pharmacokinetic interaction of cediranib 30 mg with gefitinib 250 mg (part A2; n = 15) or 500 mg (part B2; n = 15). The primary objective was to assess the safety and tolerability of cediranib with gefitinib. Secondary assessments included pharmacokinetics, efficacy and pharmacodynamics.ResultsCombination treatment was generally well tolerated; the protocol-defined maximum-tolerated dose of cediranib was 30 mg/day with gefitinib 250 mg/day (part A1) and cediranib 45 mg/day was the maximum dose investigated with gefitinib 500 mg/day (part B1). The most common adverse events were diarrhoea (84 [93%]), anorexia (63 [70%]) and fatigue (60 [67%]). Cediranib pharmacokinetic parameters were not substantially different when given alone or in combination with gefitinib. Gefitinib pharmacokinetic parameters were similar to those seen previously with gefitinib monotherapy. Efficacy results included eight (9%) confirmed partial responses (6 renal; 1 lung; 1 osteosarcoma) and 38 (42%) patients with stable disease. Pharmacodynamic assessments demonstrated changes in levels of VEGF and soluble VEGFR-2 following treatment.ConclusionsCombination treatment was generally well tolerated and showed encouraging antitumour activity in patients with advanced solid tumours. These results merit further exploration.     

Late hepatic toxicity after breast cancer intensity-modulated radiotherapy using helicoidal tomotherapy

PurposeHelical tomotherapy (HT) is a rotational intensity-modulated radiation therapy (IMRT) technique that allows target conformal irradiation and efficient organs at risk (OAR) sparing in the case of complex target volumes and specific anatomic considerations, but increases the “low-dose bath” to non-target volumes. The aim of this study was to analyze the delayed hepatotoxicity after rotational IMRT (HT) radiation therapy for non-metastatic breast cancer.Patients and methodsThis single-center retrospective study included all non-metastatic breast cancer patients with a normal pre-radiotherapy biological hepatic function who were treated with tomotherapy between January 2010 and January 2021 and for whom the dosimetric parameters for the whole liver were assessable. A logistic regression analysis was employed. The selected covariates for the multivariate analysis were those with a P-value that was less or equal to 0.20 in the univariate analysis.ResultsForty-nine patients were included in this study: 11 patients (22%) received Trastuzumab for 1 year in tumors with an HER2-expression; 27 patients (55%) received radiation therapy for cancer of the right or bilateral breasts; 43 patients (88%) received lymph node irradiation and 41 patients (84%) received a tumor bed boost. Mean and maximum doses to the liver were 2.8 Gy [0.3–16.6] and 26.9 Gy [0.7–51.7], respectively. With a median follow-up after irradiation was 5.4 years (range, 6 to 115 months), 11 patients (22%) had developed delayed low grade biological hepatic abnormalities: all patients had grade 1 delayed hepatotoxicity; 3 patients (6%) had additional grade 2 delayed hepatotoxicity. There was no hepatotoxicity at grade 3 or higher. According to the univariate and multivariate analysis, Trastuzumab was a significant predictive variable of late biological hepatotoxicity (OR = 4.4 [1.01–20.18], P = 0.04). No other variable was statistically associated with delayed biological hepatotoxicity.ConclusionDelayed hepatotoxicity after multimodal non-metastatic breast cancer management including rotational IMRT was negligible. Consequently, the liver doesn’t have to be considered like an organ-at-risk in the analysis of breast cancer radiotherapy but future prospectives studies are needed to confirm these findings.     

What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer

PurposeConcomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders.MethodsAmong the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1 cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities.ResultsFifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3–4 toxicities were reported in 10.4% and urinary grades 3–4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (> 55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P = 0.021 and P = 0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P = 0.046, odds ratio = 7.0).ConclusionsAlthough immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation. Adenocarcinoma might require higher high-risk clinical target volume planning aims.     

Five-fraction HDR brachytherapy in locally advanced cervical cancer: A monocentric experience

PurposeThe 5-fraction scheme (5 × 5–5.5 Gy) is a common High-Dose Rate (HDR) intracavitary brachytherapy regimen for locally advanced cervical cancer (LACC). Yet, its equivalence with Pulse-Dose rate (PDR) schemes remains unproved. The present study aimed at reporting on the outcome of LACC patients treated with 5-fraction HDR brachytherapy.Materials and methodsThe medical records of all consecutive patients treated with curative-intent HDR brachytherapy for a LACC in a French Cancer Center were retrospectively reviewed.ResultsThirty-eight LACC patients underwent a 5-fraction intracavitary HDR brachytherapy between 2015 and 2019 (median dose = 25 Gy/5 fractions, following external-beam radiotherapy). Median age at diagnosis was 60 (range: 29–87). Thirty-one patients (81.5%) underwent concurrent chemotherapy. Tumor stages ranged from 3 IB2 (7.8%), 4 IB3 (10.5%), 4 IIA2 (10.5%), 12 IIB (31.7%), 1 IIIA (2.6%), 2 IIIB (5.3%), 7 IIIC1 (18.5%), 4 IIIC2 (10.5%), 1 IVA (2.6%) (2018 FIGO). Median D90% to CTV_HR reached 79.5 Gy (EQD2). Median D90% to CTV_IR reached 59.5 Gy (EQD2). Median Bladder D2cc was 69.8 Gy (EQD2). Median Rectum D2cc was 58.3 Gy (EQD2). Acute/late grade 3 toxicity was reported in one patient (2.6%). No grade 4–5 toxicity occurred. At a median 38 months follow-up, 10 patients (26.3%) had local (n = 7, 18.4%), nodal (n = 6, 15.7%) and/or distant (n = 7, 18.4%) relapse. Three-year overall survival rate was of 81.6%.ConclusionThe 5-fraction HDR scheme was well tolerated even in frail patients. Three-year local control was lower than expected. Treatment (absence of parametrial interstitial implants and use of cervical EBRT boost) and patients’ characteristics (age, comorbidities) may explain such results.