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BACKGROUND: Locally advanced non-small cell lung cancer (LA-NSCLC) reported poor 5-year survival rates with frequent local or regional recurrences. Personalized RT may contribute to improve control and clinical outcome. We investigated efficacy and tolerance of "Mid-position" (Mid-P) strategy versus the conventional Internal Target Volume (ITV) strategy in LA-NSCLC patients treated by definitive conformal radiotherapy. METHODS: This prospective non-comparative randomized monocentric phase II trial included adult patients with non-resected, non-metastatic, non-previously irradiated proven LA-NSCLC treated with definitive normo-fractionated conformal radiotherapy (+/- chemotherapy). Allocated patients (randomisation 2:1) were treated using Mid-P or ITV strategy. A Fleming single-stage design (1-sided α = 0.1, 80 % power, P0 = 30 %, P1 = 50 %) planned enrolment of 36 patients in the Mid-P group. The ITV group ensured the absence of selection bias. The primary outcome was 1-year progression-free- survival (1y-PFS) rate. RESULTS: Among 54 eligible patients included from September 2012 to May 2018, 51 patients were analyzed (Mid-P: N = 34; ITV: 17). The 1y-PFS was 38 % (1-sided 95 %CI 25 %-not reached) with Mid-P strategy, and 47 % (95 %CI [27 %-not reached[) with ITV. Loco-regional failure as first event mainly occurred within radiation-field regardless the strategy. Acute and middle-term radiation toxicities were observed with both strategies. CONCLUSION: Local control and survival remain poor using the Mid-P strategy in this prospective randomized non-comparative monocentric study investigating Mid-P strategy versus ITV strategy in LA-NSCLC. Since the Mid-P strategy is not integrated into routine software, and perceived as a time-consuming method, Mid-P strategy cannot be recommended in LA-NSCLCC treated by definitive normo-fractionated conformal radiotherapy outside clinical trials.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radioterapia Conformacional , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Radioterapia Conformacional/métodos , Radioterapia Conformacional/efectos adversos , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The results of the PRODIGE 42/GERICO 12 study showed that short course radiotherapy had a better tolerance profile than radiochemotherapy, with comparable oncological results. We have included Quality of Life analyses and oncogeriatric evaluations in this study. PATIENTS AND METHODS: In all, 101 patients ≥75 years of age with resectable T3-T4 rectal adenocarcinoma less than 12 cm from the anal margin received short course radiotherapy (5X5 Gy in one week) or radiochemotherapy (50 Gy, 2 y/f and capecitabine 800 mg/m2, 5 days/week) with delayed surgery (7 weeks ± 1) in both groups. The Quality of Life analyses (EORTC QLQ C-30 et ELD14) were conducted upon inclusion, pre-operatively, at 3, 6 and 12 months post-op, together with the oncogeriatric evaluations, including an evaluation of the IADL and ADL scores, walking speed, GDS15, MMSE, MNA. RESULTS: We did not highlight any statistical difference for the global EORTC QLQ-C30 score; several factors are statistically in favor of the short course radiotherapy group at 3 months post-op (cognitive functions, fatigue, appetite). In the case of the ELD14 score, the disease burden is perceived as more negative at 3, 6 and 12 months postop in the radiochemotherapy group. The IADL score deteriorated in 44.8 % of the radiochemotherapy group and 14.8 % of the radiotherapy group (p = 0.032); similarly, the GDS15 depression score was better preserved in the short course radiotherapy group (p = 0.05). An analysis of the other scores: ADL, walking speed, MNA, MMSE did not highlight any statistical difference. CONCLUSION: Short course radiotherapy achieves better results in terms of Quality of Life and preservation of autonomy in patients aged ≥75 treated for locally advanced rectal cancer.
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Neoplasias Primarias Secundarias , Neoplasias del Recto , Anciano , Humanos , Calidad de Vida , Evaluación Geriátrica , Terapia Neoadyuvante/efectos adversos , Quimioradioterapia/métodos , Neoplasias del Recto/patología , Neoplasias Primarias Secundarias/etiología , Estadificación de NeoplasiasRESUMEN
AIM: Nonsurgical treatment with chemoradiotherapy for rectal cancer is gaining interest as it avoids total mesorectal excision (TME) surgery and stoma. The OPERA trial aims to evaluate whether dose escalation with contact X-ray brachytherapy (CXB) boost improves organ preservation compared to external beam radiotherapy (EBRT) boost. It has been suggested that dose escalation adversely affects surgical outcomes and therefore we report outcomes following TME in OPERA at 36 months. METHODS: OPERA is a European multicentre phase 3 trial (NCT02505750) which randomises patients with cT2-3a-b, cN0-1, M0 to EBCRT (45 Gy in 25 fractions over 5 weeks with oral capecitabine 825 mg/m2 ) followed by EBRT boost (9 Gy in 5 fractions over 5 days) versus EBCRT followed by CXB boost (90 Gy in 3 fractions over 4 weeks). Patients were assessed at 14, 20 and 24 weeks from the start of treatment. Watch and wait management was adopted for patients who achieved a clinical complete response (cCR) at 24 weeks following treatment. Either local excision (LE) or TME surgery was offered for residual disease or local regrowth, according to patient and surgeon preference. Surgical morbidity and mortality were recorded prospectively. RESULTS: Between July 2015 and June 2020, 148 patients were randomised of which 141 were evaluable in March 2022. At median follow-up of 38.2 months (range: 34.2-42.5), surgery was performed for 66 (47%) patients. A total of 27 (20%) patients had local excision and 39 (29%) had TME surgery, 22/39 (56%) underwent anterior resection and 17/39 (44%) underwent abdominoperineal excision of the rectum. The R0 resection rate was 87%. There were no deaths, and six patients (15%) had Clavien-Dindo IIIb complications. Whilst there was a statistically significant decrease in the TME rate following CXB boost (HR 0.38, 95% CI: 0.19-0.74, p = 0.00419) there was no difference in surgical outcomes between patients who received EBRT and CXB boost. CONCLUSION: Dose escalation can facilitate nonsurgical treatment for cT2-3 rectal cancer patients who are fit but wish to avoid TME surgery and stoma. If TME surgery is required, then it can be performed safely and effectively.
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Adenocarcinoma , Neoplasias del Recto , Humanos , Preservación de Órganos , Terapia Neoadyuvante , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Quimioradioterapia , Resultado del Tratamiento , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Recurrencia Local de NeoplasiaRESUMEN
In unresectable stage III non-small cell lung cancer (NSCLC), the standard of care for most fit patients is concurrent chemotherapy with normofractionated radiotherapy (NFRT), followed by durvalumab consolidation. Nevertheless, almost half of patients will present locoregional or metastatic intrathoracic relapse. Improving locoregional control thus remains an important objective. For this purpose, stereotactic body radiotherapy (SBRT) may be a relevant treatment modality. We performed a systematic review of the literature that evaluate the efficacy and safety of SBRT in this situation, either instead of or in addition to NFRT. Among 1788 unique reports, 18 met the inclusion criteria. They included 447 patients and were mainly prospective (n = 10, including 5 phase 2 trials). In none, maintenance durvalumab was administered. Most reported SBRT boost after NFRT (n = 8), or definitive tumor and nodal SBRT (n = 7). Median OS varied from 10 to 52 months, due to the heterogeneity of the included populations and according to treatment regimen. The rate of severe side effects was low, with <5 % grade 5 toxicity, and mainly observed when mediastinal SBRT was performed without dose constraints to the proximal bronchovascular tree. It was suggested that a biologically effective dose higher than 112.3 Gy may increase locoregional control. SBRT for selected stage III NSCLC bears potential to improve loco-regional tumor control, but at present, this should only be done in prospective clinical trials.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radiocirugia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Radiocirugia/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Prospectivos , Recurrencia Local de Neoplasia/etiologíaRESUMEN
BACKGROUND: Stereotactic ablative radiotherapy (SABR) is a validated treatment for early stage lung cancer and pulmonary metastases. It provides a high local control rate with low symptomatic toxicities. Recently, Dynamic Conformal Arc Therapy (DCAT), a delivery option that differs from conventional DCA, has been implemented in the Monaco Treatment Planning System for SABR. The aim of the study was to report clinical outcomes and toxicities for patients treated for lung SABR with this new technique. METHODS: We retrospectively identified adult patients treated for primary or secondary lung tumors with DCAT-SABR and reported their clinical, radiological, histological characteristics and dosimetric parameters. Total dose was delivered in 3 or 5 fractions for 95% of patients and prescribed on the 80% isodose line to the PTV periphery. RESULTS: 145 patients met inclusion criteria for a total of 152 lesions with a median follow up of 12 months. Local control for the irradiated site was 96.7% at 1 year. Overall survival was 93.1% at 1 year. Mean prescription dose in BED10 was 110 Gy. 92% of patients had a prescribed dose superior to 100 Gy BED10. Mean PTV coverage was 95.1%. There were 66 cases of grade 1 radiation pneumonitis (RP) (43%) and only 7 cases of symptomatic grade 2 RP (4.6%). CONCLUSION: Lung SABR for primary or metastatic lung tumors using dynamic conformal arc therapy provides efficient results of local control and low lung toxicities, similar to other SABR techniques. ADVANCES IN KNOWLEDGE: SABR using DCAT is a safe technique to treat lung lesions, allowing intra-fraction motion limitation, potentially higher OARs protection and a shortened beam delivery.
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Neoplasias Pulmonares , Neumonitis por Radiación , Radiocirugia , Adulto , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Planificación de la Radioterapia Asistida por Computador/métodos , Pulmón/patología , Neoplasias Pulmonares/radioterapia , Radiocirugia/métodos , Neumonitis por Radiación/etiologíaRESUMEN
BACKGROUND: There is no specific guideline for the treatment of locally advanced rectal cancers in the elderly. Here we compared R0 resection rate and degradation of autonomy based on the instrumental activities of daily living score between neoadjuvant, short course radiotherapy and chemoradiotherapy in this specific population. PATIENTS AND METHODS: Patients ≥75 years with resectable T3-T4 rectal adenocarcinoma within 12 cm of the anal verge or T2 of the very low rectum were randomised between short course radiotherapy (5 × 5 Gy in one week) and chemoradiotherapy (50 Gy, 2 Gy/f, 5 weeks with capecitabine: 800 mg/m2 twice daily, 5 days per week), with delayed surgery 7 ± 1 weeks for the two arms. RESULTS: One hundred and three eligible patients were enrolled between January 2016 and December 2019 when the trial was closed due to poor accrual. The R0 resection rate (first co-primary objective) was 84.3%; confidence interval 95% [73.26-94.18] in the short course group and 88%; confidence interval 95% [77.77-96.60] in the chemoradiotherapy group (non-inferiority p = 0.28). The deterioration of the instrumental activities of daily living score was not different during the pre-operative phase, it was significantly more deteriorated in the chemoradiotherapy group at 3 months post-operative (44.8% versus 14.8%; p = 0.032) but was not different at 12 months post-operative (second co-primary objective). During pre-operative phase, 9.8% of patients in short course group and 22% of patients in chemoradiotherapy group presented a serious adverse event, but we observed no difference during the post-operative phase between the two groups. CONCLUSION: Although the main objectives of the study were not achieved, the short course radiotherapy followed by delayed surgery could represent a preferred treatment option in patients ≥75 years with locally advanced rectal cancer; a new study must be performed to confirm the improvement in overall and specific survival results.
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Neoplasias del Recto , Recto , Humanos , Anciano , Recto/patología , Actividades Cotidianas , Estadificación de Neoplasias , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Capecitabina , Neoplasias del Recto/patología , Terapia Neoadyuvante/efectos adversos , Fluorouracilo , Protocolos de Quimioterapia Combinada Antineoplásica , Resultado del TratamientoRESUMEN
Background and purpose: Pulmonary stereotactic treatments can be performed using dedicated linear accelerators as well as robotic-assisted units, and different strategies can be used for dose prescription. This study aimed to compare the doses received by the tumor with a gross tumor volume (GTV)-based prescription on D98%GTV using a robotic-assisted unit (method A) and planning target volume (PTV)-based prescription on D95%PTV using a dedicated linac (method B). Material & methods: Plans of 32 patients were collected for method A, and a dose of 3 × 18 Gy was prescribed using type A algorithm and recalculated using a Monte-Carlo (MC) algorithm. The plans were normalized to match D98%GTV with the mean D 98 % G T V ¯ of the cohort. The plans of 23 patients were collected for method B, and a dose of 3 × 18 Gy was prescribed to D95%PTV using a MC algorithm. A 4D-sum method was developed to estimate doses for PTV and GTV. For validation, all plans were recalculated using an independent MC double-check software. A dose harmonization on D98% GTV was determined for both methods. Results: For method A, mean doses were D2%GTV = 59.9 ± 2.1 Gy, D50%GTV = 55.6 ± 1.2 Gy, D98%GTV = 49.5 ± 0.0 Gy. For method B, the reported doses were D2%GTV = 64.6 ± 2.1 Gy, D50%GTV = 62.8 ± 1.7 Gy, and D98%GTV = 60.0 ± 1.7 Gy. The dose trade-off of D98%GTV = 55 Gy was obtained for both methods. For method A, it corresponded to a dose prescription of 3 × 20 Gy using type A algorithm, followed by rescaling to obtain D98%GTV = 55 Gy. For method B, it corresponded to a dose prescription of D95%PTV = 3 × 16.5 Gy using the MC algorithm. Conclusions: This study determined similar near-minimum doses D98% GTV of approximately 3 × 18.3 Gy (55 Gy) using a GTV-based prescription on a robotic-assisted unit (method A) and a PTV-based prescription on a dedicated linac (method B).
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OBJECTIVES: The use of stereotactic body radiotherapy (SBRT) to treat ultra-central lung tumours remains more controversial than for peripheral and central tumours. Our objective was to assess toxicities, local control (LC) rate and survival data in patients with ultra-central lung tumours treated with SBRT. METHODS: We conducted a retrospective and monocentric study about 74 patients with an ultra-central lung tumour, consecutively treated between 2012 and 2018. Ultra-central tumours were defined as tumours whose planning target volume overlapped one of the following organs at risk (OARs): the trachea, right and left main bronchi, intermediate bronchus, lobe bronchi, oesophagus, heart. RESULTS: Median follow-up was 25 months. Two patients (2.7%) showed Grade 3 toxicity. No Grade 4 or 5 toxicity was observed. 11% of patients experienced primary local relapse. LC rate was 96.7% at 1 year and 87.6% at 2 years. Median progression free survival was 12 months. Median overall survival was 31 months. CONCLUSION: SBRT for ultra-central tumours remains safe and effective as long as protecting organs at risk is treatment-planning priority. ADVANCES IN KNOWLEDGE: The present study is one of the rare to describe exclusively ultra-central tumours through real-life observational case reports. Globally, literature analysis reveals a large heterogeneity in ultra-central lung tumours definition, prescribed dose, number of fractions. In our study, patients treated with SBRT for ultra-central lung tumours experienced few Grade 3 toxicities (2.7%) and no Grade 4 or 5 toxicities, due to the highest compliance with dose constraints to OARs. LC remained efficient.
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Neoplasias Pulmonares/radioterapia , Traumatismos por Radiación/etiología , Radiocirugia/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Dosificación Radioterapéutica , Estudios Retrospectivos , Adulto JovenRESUMEN
Concomitant radiochemotherapy (RTCT) is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, in patients with a peripheral primary tumor, the irradiated volume may include a large portion of normal lung and RT-CT is not possible. This multicenter phase II trial in unresectable stage III NSCLC with peripheral primary tumor evaluated the feasibility of stereotactic body radiation therapy (SBRT) in peripheral tumor after concomitant radio-chemotherapy (RT-CT). Nineteen patients were included and analyzed (median age, 60.9 years; male, 78%; adenocarcinoma, 74%; median size of peripheral primary tumor, 19 mm). At 6 months, the disease control rate was 79% (15/19). SBRT toxicity was generally mild with one (5%) patient having grade 3 lung toxicity. Recruitment for this study was stopped prior to completion, firstly due to the approval of adjuvant durvalumab after RT-CT, which was not anticipated in the design, and secondly due to the small number of stage III NSCLC patients with a peripheral tumor that was accessible to SBRT. Nevertheless, the combination of RT-CT and SBRT appeared to be feasible and safe.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radiocirugia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Estudios de Factibilidad , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To assess the relevance of virtual reality distraction (VR) during uterovaginal brachytherapy applicators' removal, as an alternative to nitrous oxide (N2O) conscious sedation, to decrease anxiety and pain perception. METHODS AND MATERIALS: We prospectively evaluated 35 patients treated with cervical brachytherapy for locally or locally advanced cervical cancer. Brachytherapy applicators were removed in the patient's room at the end of the treatment. Patients were assigned to N2O conscious sedation (reference group) or VR (experimental group). Anxiety and pain were evaluated with the STAI-E score and with Visual Analogical Scales (VAS). RESULTS: Fourteen patients were treated with VR and 21 with N2O. STAI-E baselines scores were 35 in the VR group and 38 in the reference group and declined to 30 and 28, respectively after procedure. The mean VAS-anxiety was 2.9 before and 2.7 at the peak in the VR group versus 4.1 and 1.6, respectively in the reference group. The mean VAS-pain was 1.0 before, 3.1 at the peak and 0.4 after the procedure in the experimental group, versus 1.8, 2.0, and 0.6 respectively in the N2O group. Four patients in the VR group experienced mild nausea/vomiting or dizziness during the procedure. The preparation duration was higher in the VR group, with a similar duration for the removal itself. CONCLUSIONS: Replacing a medical gas by a virtual reality device was feasible and led to acceptable levels of pain and anxiety. Prospective randomized trials are needed to confirm efficacy and to determine which patients could benefit the most from this approach.
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Braquiterapia , Realidad Virtual , Braquiterapia/métodos , Humanos , Dolor , Dimensión del Dolor , Estudios ProspectivosRESUMEN
Background: Stereotactic body radiotherapy (SBRT) is a recognized treatment for colorectal cancer (CRC) metastases. We postulated that local responses could be improved by SBRT with a concomitant radiosensitizing agent (irinotecan). Methods: RADIOSTEREO-CAMPTO was a prospective multi-center phase 2 trial investigating SBRT (40-48 Gy in 4 fractions) for liver and/or lung inoperable CRC oligometastases (≤3), combined with two weekly intravenous infusions of 40 mg/m2 Irinotecan. Primary outcome was the objective local response rate as per RECIST. Secondary outcomes were early and late toxicities, EORTC QLQ-C30 quality of life, local control and overall survival. Results: Forty-four patients with 51 lesions (liver = 39, lungs = 12) were included. Median age was 69 years (46-84); 37 patients (84%) had received at least two prior chemotherapy treatments. Median follow-up was 48.9 months. One patient with two lung lesions was lost during follow-up. Assuming maximum bias hypothesis, the objective local response rate in ITT was 86.3% (44/51-95% CI: [76.8-95.7]) or 82.4% (42/51-95% CI: [71.9-92.8]). The observed local response rate was 85.7% (42/49-95% CI: [75.9-95.5]). The 1 and 2-year local (distant) progression-free survivals were 84.2% (38.4%) and 67.4% (21.3%), respectively. The 1 and 2-year overall survivals were 97.5% and 75.5%. There were no severe acute or late reactions. The EORTC questionnaire scores did not significantly worsen during or after treatment. Conclusions: SBRT with irinotecan was well tolerated with promising results despite heavily pretreated patients.
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OBJECTIVES: This prospective, observational, non-randomized multicentric study was conducted to compare efficiency and toxicity using different modalities of stereotactic body radiation therapy (SBRT) in early-stage peripheral non-small cell lung cancer (NSCLC). METHODS: From 9 April to 11 December, 106 patients were treated according to the local equipment availability for peripheral NSCLC with SBRT: 68 by linear accelerator equipped for SBRT and 38 by Cyberknife®. Multivariate analysis and propensity score analysis using Inverse Probability Treatment Weighting (IPTW) were undertaken in an effort to adjust for potential bias due to non-randomization. RESULTS: 2-year local control rates were 97.0% (95% CI: [90.6%; 99.4%]) with SBRT by Linac vs 100% (95% CI: ([100%; 100%]) with Cyberknife® (p = 0.2839). 2-year PFS and 2-year OS rates were 52.7% (95% CI [39.9%;64.0%]) versus 54.1% (95% CI [36.8; 68.6%]) (p = 0.8582) and 65.1% (95% CI: [51.9%; 75.5%] versus 83.9% (95% CI: [67.5%; 92.4%] (p = 0.0831) using Linac and Cyberknife® respectively. Multivariate regression analysis indicates no significant effect of SBRT treatment type on PFS or OS. Local relapse could not be modeled due to the small number of events (n = 2). Acute and late toxicity rates were not significantly different. After IPTW adjustment, results were unchanged. CONCLUSIONS: No difference in efficiency or toxicity was shown after SBRT of peripheral NSCLC treatment using Linac or Cyberknife®. ADVANCES IN KNOWLEDGE: This is the first large prospective non-randomized study focusing on peripheral localized NSCLC comparing SBRT using an appropriately equipped linac with Cyberknife®. No significant difference in efficiency or toxicity was shown in this situation.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirugia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Francia , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Stereotactic irradiation (SBRT) is a standard of care for inoperable stage I lung cancer and brain oligometastases from lung cancer but is controversial for extracranial oligometastases. We assessed outcomes of lung cancer patients with extracranial metastases in oligometastatic, oligorecurrent, oligopersistent and oligoprogressive settings ("oligometastatic spectrum") under strategies using SBRT +/- systemic treatments. METHODS: A retrospective multicentric study of consecutive lung cancer adult patients with 1-5 extracranial metastases treated with SBRT was conducted. RESULTS: Of 91 patients (99 metastases, median age 63, 64.8% adenocarcinomas, 19.8% molecular alterations), 11% had oligometastases, 49.5% oligorecurrence, 19.8% oligopersistence and 19.8% oligoprogression. Of 36% of patients under systemic treatments at initiation of SBRT, systemic treatment interruption was performed in 58% of them. With median follow up of 15.3 months, crude local control at irradiated metastases was 91%, while median distant progression-free survival (dPFS) and overall survival were 6.3 and 28.4 months (2-year survival 54%). Initial nodal stage and oligometastatic spectrum were prognostic factors for dPFS; age, initial primary stage and oligometastatic spectrum were prognostic factors for survival on multivariate analysis. Patients with oncogene-addicted tumors more frequently had oligoprogressive disease. Repeat ablative irradiations were preformed in 80% of patients who had oligorelapses. Worst acute toxicities consisted of 5.5% and one late toxic death occurred. CONCLUSION: The oligometastatic spectrum is a strong prognosticator in patients undergoing SBRT for extracranial metastases. Median survival was over two years but dPFS was about 6 months. Continuation of systemic therapy in oligoprogressive patients should be investigated.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Radiocirugia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: The impact of the dose and fractionation of thoracic radiotherapy on the risk of developing brain metastasis (BM) has not been evaluated prospectively in limited stage SCLC patients receiving prophylactic cerebral irradiation (PCI). METHODS: Data from patients treated with PCI from the CONVERT trial were analyzed. RESULTS: Four hundred forty-nine of 547 patients (82%) received PCI after completion of chemoradiotherapy. Baseline brain imaging consisted of computed tomographic scans in 356 of 449 patients (79%) and magnetic resonance imaging in 83 of 449 (18%) patients. PCI was delivered to 220 of 273 participants (81%) in the twice-daily (BD) group and 229 of 270 in the once-daily (OD) group (85%; p = 0.49). Total median PCI dose was 25 Gy in both the BD and OD groups (p = 0.74). In patients who received PCI, 75 (17%) developed BM (35 [8%] in OD and 40 [9%] in BD) and 173 (39%) other extracranial progression. In the univariate analysis, gross tumor volume (GTV) was associated with an increased risk of BM (p = 0.007) or other radiological progression events (p = 0.006), whereas in a multivariate analysis both thoracic GTV (tGTV) and ECOG performance score were associated with either progression type. The median overall survival (OS) of patients treated with PCI was 29 months. In the univariate analysis of OS, PCI timing from end of chemotherapy, weight loss of more than 10%, and tGTV were prognostic factors associated with OS. In the multivariate analysis, only tGTV was associated with OS. Delay between end of chemotherapy and PCI was not associated with OS. CONCLUSIONS: Patients receiving OD or BD thoracic radiotherapy have the same risk of developing BM. Larger tumors are associated with a higher risk of BM.
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Neoplasias Encefálicas/prevención & control , Irradiación Craneana , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células Pequeñas/terapia , Carga Tumoral , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Quimioradioterapia , Progresión de la Enfermedad , Fraccionamiento de la Dosis de Radiación , Humanos , Neoplasias Pulmonares/patología , Imagen por Resonancia Magnética , Estadificación de Neoplasias , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Carcinoma Pulmonar de Células Pequeñas/secundario , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: There is a lack of data on the efficacy and safety of concurrent chemoradiotherapy in elderly, limited-stage, patients with SCLC. METHODS: We compared outcomes of patients 70 years of age or older versus younger patients within the Concurrent Once-daily Versus twice-daily RadioTherapy (CONVERT) trial. Patients were randomized to receive 45 Gy/30 twice-daily fractions/19 days or 66 Gy/33 once-daily fractions/45 days concurrently with platinum-based chemotherapy. Overall survival and progression-free survival were evaluated using Kaplan-Meier methodology and Cox proportional hazards regression. RESULTS: Of 547 patients randomized between April 2008 and November 2013, 57 did not receive protocol treatment and were excluded. Of the 490 patients included, 67 (14%) were 70 years of age or older (median age: 73 years; range: 70-82). Fewer older patients received the optimal number of radiotherapy fractions (73% versus 85%; p = 0.03); however, chemotherapy compliance was similar in both groups (p = 0.24). Neutropenia grade 3/4 occurred more frequently in the elderly (84% versus 70%; p = 0.02) but rates of neutropenic sepsis (4% versus 7%; p = 0.07) and death (3% versus 1.4%; p = 0.67) were similar in both groups. With a median follow-up of 46 months; median survival in the elderly versus younger groups was 29 (95% confidence interval [CI]: 21-39) versus 30 months (95% CI: 26-35), respectively; (hazard ratio: 1.15, 95% CI: 0.84-1.59; p = 0.38). Median time to progression in the elderly versus younger groups was 18 months (95% CI: 13-31) versus 16 months (95% CI: 14-19), respectively (hazard ratio: 1.04, 95% CI: 0.76-1.41; p = 0.81). CONCLUSIONS: Concurrent chemoradiotherapy with modern radiotherapy techniques should be a treatment option for fit, older patients.
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Neoplasias Pulmonares/radioterapia , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
PURPOSE: Whereas post-radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistant and genetic hyperradiosensitive cases. METHODS AND MATERIALS: Immunofluorescence experiments were performed on a collection of skin fibroblasts from 12 radioresistant, 5 hyperradiosensitive, and 100 OR patients irradiated at 2 Gy. The numbers of micronuclei, γH2AX, and pATM foci that reflect different steps of DNA double-strand breaks (DSB) recognition and repair were assessed from 10 minutes to 24 hours after irradiation and plotted against the severity grades established by the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group. RESULTS: OR patients did not necessarily show a gross DSB repair defect but a systematic delay in the nucleoshuttling of the ATM protein required for complete DSB recognition. Among the radiobiological factors, the maximal number of pATM foci provided the best discrimination among OR patients and a significant correlation with each OR severity grade, independently of tumor localization and of the early or late nature of reactions. CONCLUSIONS: Our results are consistent with a general classification of human radiosensitivity based on 3 groups: radioresistance (group I); moderate radiosensitivity caused by delay of nucleoshuttling of ATM, which includes OR patients (group II); and hyperradiosensitivity caused by a gross DSB repair defect, which includes fatal cases (group III).
Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Núcleo Celular/metabolismo , Roturas del ADN de Doble Cadena , Histonas/metabolismo , Traumatismos por Radiación/clasificación , Tolerancia a Radiación/fisiología , Piel/efectos de la radiación , Análisis de Varianza , Proteínas de la Ataxia Telangiectasia Mutada/genética , Biopsia , Línea Celular , Reparación del ADN , Fibroblastos/efectos de la radiación , Humanos , Pruebas de Micronúcleos/métodos , Fosforilación , Traumatismos por Radiación/metabolismo , Traumatismos por Radiación/patología , Tolerancia a Radiación/genética , Piel/patología , Factores de TiempoRESUMEN
PURPOSE: The objective of this randomised phase II study was to evaluate the impact in terms of response and toxicities of induction or consolidation chemotherapy respectively before or after concurrent chemoradiotherapy in unresectable stage III non-small-cell lung cancer. PATIENTS AND METHODS: In the induction arm, patients received induction chemotherapy with cisplatin (80 mg/m(2)) and paclitaxel (200 mg/m(2)) on days 1 and 29 followed by a concurrent chemoradiotherapy (66 Gy in 33 fractions, cisplatin 80 mg/m(2) days 1, 29 and 57, vinorelbine 15 mg/m(2) days 1, 8, 29, 36, 57 and 64). In consolidation arm, the same concurrent chemoradiotherapy began on day 1 followed by two cycles of cisplatin and paclitaxel. RESULTS: One hundred twenty seven patients were randomised. The intent to treat response rates in induction and consolidation arms were 58% and 56% respectively. Median survival was 19.6 months in induction arm and 16.3 months in consolidation arm and 4-year survival rates were 21% and 30% respectively. Haematologic and non-haematologic toxicities were similar in both arms, except grade 3/4 oesophagitis, more frequent in consolidation arm than in induction arm (17% versus 10%). CONCLUSION: Cisplatin-based chemotherapy as induction or consolidation with concurrent chemoradiotherapy can be administrated safely. Response rates were similar in both arms with a trend in favour for consolidation arm for long-term survival.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/métodos , Quimioterapia de Consolidación/métodos , Quimioterapia de Inducción/métodos , Neoplasias Pulmonares/terapia , Estadificación de Neoplasias , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioradioterapia/efectos adversos , Quimioradioterapia/mortalidad , Cisplatino/uso terapéutico , Quimioterapia de Consolidación/efectos adversos , Quimioterapia de Consolidación/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/mortalidad , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Dosificación Radioterapéutica , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Vinblastina/análogos & derivados , Vinblastina/uso terapéutico , VinorelbinaRESUMEN
BACKGROUND: Radiochemotherapy without surgical resection has become the treatment of choice for anal squamous-cell carcinoma. The optimal treatment for rectal squamous-cell carcinoma is not well established. OBJECTIVE: The purpose of this work was to assess the efficacy of nonoperative strategies in the management of primary rectal squamous-cell carcinoma. DESIGN: We retrospectively reviewed data from all of the patients with documented rectal squamous-cell carcinoma who were treated with conservative strategies in a single institution. Concomitant radiochemotherapy was proposed to all except 1 patient. The remaining patient was treated by radiotherapy alone given his impaired functional status. All of the patients were treated with conformal or intensity-modulated radiation therapy. Surgical resection was reserved for persistent disease or relapse. SETTING: This study was conducted in a single tertiary institution. MAIN OUTCOME MEASURES: After a mean follow-up of 56 months, 2 patients experienced relapse and no patients died. RESULTS: Eleven patients were included in the series. The clinical response to radiotherapy was complete for 7 patients. The remaining 4 patients underwent salvage surgery. The pathologic response was incomplete for 2 of the 4 patients. One recurrence occurred outside the field of radiotherapy and was successfully treated by radiotherapy. The second was a local recurrence, which occurred on a patient who was treated with radiotherapy alone. LIMITATIONS: The number of patients included in this retrospective series was limited because of the rarity of the disease. Patients were treated with nonhomogeneous conservative strategies because of modification in the therapeutic strategy for anal squamous-cell carcinoma and of the adaptation of the treatment to patient comorbidities and functional status. CONCLUSIONS: This series demonstrates that good results can be obtained by using a rectum-conserving strategy. Close follow-up should be maintained, with the use of salvage surgery reserved only for persistent disease or relapse (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A155).
Asunto(s)
Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Neoplasias del Recto/terapia , Anciano , Anciano de 80 o más Años , Biopsia , Carcinoma de Células Escamosas/patología , Colonoscopía , Endosonografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias del Recto/patología , Estudios Retrospectivos , Terapia Recuperativa , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer. METHODS: We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I-IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0-2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), bolus fluorouracil 400 mg/m(2), and infusional fluorouracil 1600 mg/m(2) (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m(2) per day for 4 days and cisplatin 75 mg/m(2) on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094. FINDINGS: 134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9-36·4). Median progression-free survival was 9·7 months (95% CI 8·1-14·5) in the FOLFOX group and 9·4 months (8·1-10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70-1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil-cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin-fluorouracil group, p<0·0001), sensory neuropathy (24 [18%] vs one [1%], p<0·0001), increases in aspartate aminotransferase concentrations (14 [11%] vs two [2%], p=0·002), and increases in alanine aminotransferase concentrations (11 [8%] vs two [2%], p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four [3%] vs 15 [12%], p=0·007), mucositis (35 [27%] vs 41 [32%], p=0·011), and alopecia (two [2%] vs 12 [9%], p=0·005) were more common in the fluorouracil and cisplatin group. INTERPRETATION: Although chemoradiotherapy with FOLFOX did not increase progression-free survival compared with chemoradiotherapy with fluorouracil and cisplatin, FOLFOX might be a more convenient option for patients with localised oesophageal cancer unsuitable for surgery. FUNDING: UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer.