Stereotactic body radiation therapy to postpone systemic therapy escalation for castration-resistant prostate cancer: A multicenter retrospective analysis.

Purpose: To evaluate the oncological outcome after stereotactic body radiation therapy (SBRT) for oligoprogressive metastatic castration-resistant prostate cancer (omCRPC) patients. Materials-Methods: In this retrospective, observational, multi-institutional study, omCRPC patients (≤5 metastases) underwent SBRT. Primary endpoint was systemic therapy escalation-free survival (STE-FS) after SBRT. Local relapse (LR), distant (DP) and isolated biochemical (iBP) progressions were reported with progression-free survival (PFS) and overall survival (OS). Prognostic factors for STE-FS were investigated. Toxicity was reported. Results: From 01/07 to 09/19, 50 pts with omCRPC underwent SBRT. With a MFU of 23 months [3---100], median STE-FS was 13.1 months (95 %CI 10.8 - 36.4). Median OS was not reached and PFS was 13 months (CI95% 10.1 - 20.8). Post-SBRT PSA remained stable or decreased in 19 pts (38 %). Progression events (LR, DP, iBP) were observed in 34 pts (68 %), among whom 6 relapsed in the irradiated area (local control rate: 88 %). DP and iBP were observed in 28 pts (56 %) and 4 pts (8 %) respectively. In multivariate analysis, post-SBRT biochemical response was an independent prognostic factor for STE-FS. Grade ≥ 3 toxicity occurred in 2 pts. Conclusion: With excellent local control and tolerance, SBRT for omCRPC patients represents an acceptable approach to defer systemic therapeutic escalation and prevent its side effects. Accurate patient selection for SBRT requires more data with longer follow-up and higher numbers of patients pending the results of upcoming randomized trials.

Systemic therapy escalation after stereotactic body radiation therapy for oligometastatic hormone-sensitive prostate cancer.

Purpose: To evaluate the oncological outcome after stereotactic body radiation therapy (SBRT) for oligometastatic hormone-sensitive prostate cancer (omHSPC) patients. Materials-Methods: In this retrospective, observational, multi-institutional study, omHSPC patients (≤5 metastases) underwent SBRT. Primary endpoint was systemic therapy escalation-free survival (STE-FS) after SBRT. Local (LR), distant (DR), prostatic (PR) and isolated biochemical (iBR) relapses were reported with progression-free survival (PFS) and overall survival (OS). Prognostic factors for STE-FS were investigated. Toxicity was reported. Results: From 01/07 to 09/19, 119 pts with omHSPC underwent SBRT. With a MFU of 34 months [12-97], median STE-FS was 33.4 months (95%CI 26.6---40.1). Median OS was not reached and PFS was 22.7 months (CI95% 18.6---32.3). Post-SBRT-PSA remained stable or decreased in 87 pts (73.1%). Progression events (LR, MR, PR, iBR) were observed in 72 pts (60.5%), among whom 6 relapsed in the irradiated area (local control rate: 95%). DR, BR, PR were observed in 44 pts (37%), 21pts (17.7%) and 2 pts (1.7%) respectively. In multivariate analysis, post-SBRT biochemical response was an independent prognostic factor for STE-FS. Grade ≥ 3 toxicity occurred in 1pt. Conclusion: With excellent local control and tolerance, SBRT for omHSPC patients represents an attractive approach to defer systemic therapeutic escalation and prevent its side effects. Accurate patient selection for SBRT requires more data with longer follow-up and higher numbers of patients pending the results of upcoming randomized trials.

High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer.

BACKGROUND: Carbonic anhydrase IX (CAIX) is an enzyme upregulated by hypoxia during tumour development and progression. This study was conducted to assess if the expression of CAIX in tumour tissue and/or plasma can be a prognostic factor in patients with non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays containing 555 NSCLC tissue samples were generated for quantification of CAIX expression. The plasma level of CAIX was determined by ELISA in 209 of these NSCLC patients and in 58 healthy individuals. The CAIX tissue immunostaining and plasma levels were correlated with clinicopathological factors and patient outcome. RESULTS: CAIX tissue overexpression correlated with shorter overall survival (OS) (P=0.05) and disease-specific survival (DSS) of patients (P=0.002). The CAIX plasma level was significantly higher in patients with NSCLC than in healthy individuals (P<0.001). A high level of CAIX in the plasma of patients was associated with shorter OS (P<0.001) and DSS (P<0.001), mostly in early stage I+II NSCLC. Multivariate Cox analyses revealed that high CAIX tissue expression (P=0.002) was a factor of poor prognosis in patients with resectable NSCLC. In addition, a high CAIX plasma level was an independent variable predicting poor OS (P<0.001) in patients with NSCLC. CONCLUSION: High expression of CAIX in tumour tissue is a predictor of worse survival, and a high CAIX plasma level is an independent prognostic biomarker in patients with NSCLC, in particular in early-stage I+II carcinomas.

[Functional stereotactic radiosurgery: Indications and perspectives]. / Radiochirurgie fonctionnelle : indications et perspectives.

Stereotactic radiosurgery (SRS) is a non-invasive technique that enables to create brain focal lesions with a high precision and localization. Thus, functional brain disorders can be treated by SRS in case of pharmacoresistance or inoperability. To date, treatment of trigeminal neuralgia is the most described and known indication. Other indications will be developed in the future like movement disorders, refractory epilepsy, obsessive compulsive disorder and severe depression. We present here a review of actual and future indications of functional brain SRS with their level of evidence. All these SRS treatments have to be strictly conducted by trained teams with an excellent collaboration between radiation physicists, medical physicists, neurosurgeons, neurologists, psychiatrists and probably neuroradiologists.

Split-course hypofractionated radiotherapy for aged and frail patients with head and neck cancers. A retrospective study of 75 cases.

PURPOSE: To assess the efficacy and the tolerance of a split course hypofractionated (SCH) radiotherapy (RT) protocol in head and neck cancer (HNC) for eldery and/or unfit patients (pts). PATIENTS AND METHODS: Pts with HNC treated by SCH-RT in two institutions were included retrospectively. The main SCH RT regimen was two courses of 30 grays (Gy)/10 fractions separated by 2-4 weeks, without any systemic therapy. RESULTS: Between February 2012 and January 2019, 75 consecutive patients were analyzed. The median age was 80 years (range: 45.7-98.2) and 53 (70.7%) were men. Sixty-one (81.3%) pts had stage III/IV disease and 54 (72%) had at least two comorbidities. All of them were treated with intensity-modulated radiotherapy. Median follow-up was 10.6 months (range: 3.1-58.3). Local control at 12 and 24 months was 72.8% IC95%[62-85.5] and 51.7% IC95%[38.1-70.1] respectively. Progression free survival (PFS) at 12 and 24 months were 47.7% IC95%[37.4-60.8] and 41% IC95%[15-36.4] respectively, with a median of 11.5 months IC95%[8.9-17]. OS at 12 and 24 months were 60.4% IC95%[50-73.1] and 41% IC95%[30.6-54.9] respectively, with a median of 19.3 months IC95%[11.9-25.8]. Acute and late grade 3 or higher toxicities occurred for 6 (8%) and 3 (4%) pts. CONCLUSION: The present SCH-RT regimen seems effective, well-tolerated and could represent an alternative to palliative strategies for pts deemed unfit for standard exclusive RT.

[Hypofractionad radiotherapy for elderly with head and neck cancer]. / Radiothérapie hypofractionnée des cancers ORL chez le sujet âgé.

Thirty percent of patients with head and neck cancer are over 70 years. Radiotherapy approach in elderly is a challenge. On one hand, radiotherapy side effects, as well as the number of sessions required, could be a burden. On the other hand, omission of local treatment is not an option due to the symptoms of the tumor. Patients in good general condition may receive standard fractionnated radiotherapy. For frail patients unsuitable for standard fractionated radiotherapy, more convenient shorter course of radiotherapy are commonly used. Physicians have to choose the best radiotherapy schedule according to the objective of the treatment. In case of palliative intend: hypofractionated radiotherapy delivered with a single short course could be recommanded. This course could be followed by other subsequent courses if the patient's condition improves during the treatment. For patients treated in curative intend, the choice of hypofractionation schedule depends on the general condition: split course hypofractionated radiotherapy for unfit patients, or accelerated radiotherapy with concomitant boost for fit patients. In all cases, a high-quality radiotherapy technique and appropriate supportive care are mandatory to minimize the side effects. The ELAN RT trial, soon to be completed, will rule on the non-inferiority of hypofractionated radiotherapy compared to standard radiotherapy for unfit patients.

State of the art and recent advance in the treatment of resectable nonmetastatic rectal cancer.

INTRODUCTION: Standard treatment is achieving good local control for rectal cancer. Innovative approach is aiming at increasing conservative treatment. METHODOLOGY: Strong evidence relies on randomized trials. Phase I and II trials are the method to evaluate advances. RESULTS: Preoperative radiotherapy with concurrent chemotherapy is the standard treatment for most of the T3 (4) tumors. To increase conservative treatment innovative neoadjuvant treatment achieving complete clinical response is a promising approach. CONCLUSION: Well-conducted clinical trials are improving the standard treatments and are evaluating new hypotheses.

French experience with contact X-ray endocavitary radiation for early rectal cancer.

This paper is an overview of the French experience with contact X-ray radiation for rectal cancer. The analysis was mainly carried out on 50 years of experience in Lyon or since 1980 in the Centre Hospitalier Universitaire Lyon Sud. The results obtained in Dijon and Nancy are also reported. In early rectal cancer, contact X-ray radiation can play an important role in three different situations: (1) small T1 less than 2 cm: adjuvant contact X-ray radiotherapy after local excision; (2) T2 N0 or large T1: first-line contact X-ray radiotherapy combined with external beam radiotherapy (+/- chemotherapy) followed by surgery (anterior resection or local excision); (3) early T3 N0 in frail patients: the same approach as for T2 N0 with, in case of clinical complete response, local excision or follow-up.

[Guide for external beam radiotherapy. Procedures 2007]. / Guide des procédures de radiothérapie externe 2007.

In order to optimize quality and security in the delivery of radiation treatment, the French SFRO (Société française de radiothérapie oncologique) is publishing a Guide for Radiotherapy. This guide is realized according to the HAS (Haute Autorité de santé) methodology of "structured experts consensus". This document is made of two parts: a general description of external beam radiation therapy and chapters describing the technical procedures of the main tumors to be irradiated (24). For each procedure, a special attention is given to dose constraints in the organs at risk. This guide will be regularly updated.

[Management of locally advanced anal canal carcinoma with modulated arctherapy and concurrent chemotherapy]. / Place de l'arcthérapie modulée et de la chimiothérapie concomitante dans la prise en charge des cancers du canal anal localement évolués.

The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed.

[Human papilloma virus in head and neck cancer]. / Papillomavirus humain et cancer ORL.

Head and neck cancer is frequently associated with alcohol and tobacco consumption but there is an increasing incidence of oropharyngeal carcinoma associated with oncogenic type-16 human papillomavirus (HPV). The clinical profile of these patients is distinct from that of other patients, with an earlier onset, 1/1 male to female sex ratio, cystic cervical nodes. Detection of intratumoral viral DNA is essential to confirm the role of HPV. According to several reports, the prognosis in terms of survival and locoregional control is better in HPV-positive oropharyngeal carcinoma than in HPV-negative oropharyngeal carcinoma or associated with tobacco consumption. The future lies in vaccination of women against cervical cancer but vaccination of boys will be certainly necessary.

[Normal tissue tolerance to external beam radiation therapy: lung]. / Dose de tolérance à l'irradiation des tissus sains: le poumon.

Radiation pneumonitis is the most common dose limiting complication of thoracic radiation. Clinically significant radiation pneumonitis usually develops in 10-20% of patients. Characteristic clinical features associated with radiation pneumonitis include dyspnea, non-productive cough, radiographic opacification confined to the outlines of the field of radiation treatment and changes in pulmonary function measures. The risk of radiation pneumonitis is related to the cumulative dose of radiation to normal tissue and to patients and tumor features. Some studies demonstrated that preexisting pulmonary lung dysfunction, tumour location in lower lobes, use of concurrent chemotherapy could increase the risk of radiation pneumonitis. Controversies persist about which dosimetric parameter optimally predicts the risk of radiation pneumonitis. Mean lung dose, V20 and V30 are the most studied parameters. However, no ideal dosimetric parameter has been identified. The objective of this review is to summarize predictive factors of radiation pneumonitis, and to evaluate the predictive ability of various dose-volume histogram parameters for routine practice.

[Normal tissue tolerance to external beam radiation therapy: salivary glands]. / Dose de tolérance à l'irradiation des tissus sains: les glandes salivaires.

Xerostomia is one of the most a common complication of radiotherapy for head and neck cancers, affecting quality of life. Parotid glands produce approximately 60% of saliva and submandibular glands 20% of saliva while the rest is secreted by sublingual and accessory salivary glands. Methods of measuring the salivary output are collection of unstimulated or stimulated saliva or 99mTc-pertechnate scintigraphy. Several studies demonstrated that late salivary dysfunction after radiotherapy has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia could be avoided if at one parotid gland is spared to a mean dose of less than approximately 25-30 Gy. Clinical benefit of submandibular gland sparing is more controversial. A mean dose less than 39 Gy could preserve submandibular gland function. This paper aims to review main studies evaluating tolerance dose of salivary glands.

[Normal tissue tolerance to external beam radiation therapy: ovaries]. / Tolérance à l'irradiation des tissus sains: les ovaires.

Clinical situations requiring protections of ovaries are mainly paediatric irradiations and pre-menopausal pelvic irradiations. The main complication of ovarian irradiation is the induced castration. Ovaries are extremely radiosensitive organs with strong interpersonal variations. The castrative effect of irradiation depends mainly on two factors: patient's age and the dose delivered to ovaries. The surgical technique of ovarian transposition allows to minimize the dose received by ovaries by taking them away, out of irradiation fields; the aim is to exclude them from the volume receiving 5 Gy or more, and if possible from those receiving 2 Gy. This technique becomes integrated into a multidisciplinary approach of conservation of fertility for patients exposed to other cytotoxic treatments.

[Normal tissue tolerance to external beam radiation therapy: testicles]. / Dose de tolérance à l'irradiation des tissus sain: les testicules.

Although there is very little evidence for direct irradiation of the testes, they may receive significant doses, especially in the treatment of pelvic tumors in adults and in pediatrics. The exocrine function of the testis seems to be more sensitive to radiotherapy. There is a risk of sterility, even after low doses of radiation. In the adult or the child who has reached puberty, we should propose a self-preservation of semen prior to radiotherapy. In pre-pubescent children, the problem is more delicate. In all cases, it is necessary to limit the dose to the testicles without affecting the coverage of tumour volume. Patients and/or their caregivers should be systematically informed of the risk of infertility related to irradiation.

[Teeth and irradiation: dental care and treatment of osteoradionecrosis after irradiation in head and neck cancer]. / Dent et irradiation: prévention et traitement des complications dentaires de la radiothérapie y compris l'ostéoradionécrose.

Pre-irradiation dental care depends on teeth health, fields and dose of irradiation, compliance to fluorides, cessation of tobacco and psychosocial cofactors. Dental care aims at preventing complications and preserving the quality of life (eating, speech, and aesthetics). The role of hyperbaric oxygenotherapy for the prevention of osteoradionecrosis after teeth removal on the mandibula in areas receiving 50 Gy or more is still controversial. Medical treatments may be sufficient for early stages of osteoradionecrosis (antibiotics, pain killers, non-steroidal anti-inflammatory drugs as well as clodronate, vitamin E, pentoxifyllin). However, reconstructive surgery should not be delayed in advanced stages of osteoradionecrosis. New irradiation techniques are changing dose distributions and therefore require close collaboration between odonto-stomatologists and radiation oncologists to define the best dental care.

[Teeth and irradiation in head and neck cancer]. / Dent et irradiation: denture et conséquences sur la denture de la radiothérapie des cancers de la tête et du cou.

Pre-irradiation dental care depends on teeth health, fields and dose of irradiation, compliance to fluorides, cessation of tobacco and psychosocial cofactors. Dental care aims at preventing complications and preserving the quality of life (eating, speech and aesthetics). Approximately 11% of patients do not require any pre-irradiation dental care. Dental complications vary from slight colorations of the teeth to major complication such as osteoradionecrosis. Osteoradionecrosis rates vary from 1 to 9%, and may be decreased by using a 21-day delay between extractions and irradiation, provided that it does not postpone cancer treatment, with a dose-dependent risk (<6% if <40 Gy; 14% between 40 et 60 Gy; > or =20% if >60 Gy). Osteoradionecrosis occurs spontaneously (35%), mostly involves the mandibula (85%).