Outcomes of radiation therapy of indolent cutaneous B-cell lymphomas and literature review.

BACKGROUND: Primary cutaneous B-cell lymphomas represent approximately 25% of primary cutaneous lymphomas. Follicular centre cell lymphomas (PCFCL) and marginal zone lymphomas (PCMZL) are the two histological subtypes that present an indolent evolution. Radiotherapy is one of the recommended treatment options with few series reported. OBJECTIVE: This study aimed to evaluate radiotherapy outcomes in term of overall survival (OS) and disease-free survival (DFS) for patients suffering from a PCMZL or PCFCL, to search for predictive factors of recurrence, and to evaluate chronic and aesthetics adverse events and patient's satisfaction. METHODS: Patients treated with contact low energy radiotherapy for a PMZCL or PCFCL from April 2009 to June 2017 in Saint Louis hospital were retrospectively analysed. Total dose ranged from 18 to 30 Gy. Objective response (OR) rates, DFS and OS as patterns of recurrence according to radiation fields were analysed. Univariate analysis of DFS has been performed according to clinical and biological parameters. Acute toxicity, long-term adverse events and satisfaction were collected via individualized questionnaires. RESULTS: Forty-six patients were included. Median follow-up was 43.5 months. OR was achieved for 100% of cases. Recurrence occurred in 39% of cases. Median DFS was 44 months. Three-year DFS and 5-year DFS were 56% and 51%, respectively. OS at 3 and 5 year was 100%. Only sex was significantly associated with DFS. Acute AEs occurred in 48% of cases without grade 3 and 4. 55% reported some moderate aesthetic sequelae for long-term AEs. 97% were satisfied with treatment. CONCLUSION: This study confirms the good risk-benefit of radiotherapy for the treatment of primary cutaneous indolent B-cell lymphomas due to the high response rate and a long DFS. No significant factor for recurrence was identified, except female sex. Long-term aesthetic evaluation was good or excellent for most of the patients.

Non-AIDS-related malignancies: expert consensus review and practical applications from the multidisciplinary CANCERVIH Working Group.

Malignancies represent a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The introduction of combined antiretroviral therapy has modified the spectrum of malignancies in HIV infection with a decreased incidence of acquired immunodeficiency syndrome (AIDS) malignancies such as Kaposi's sarcoma and non-Hodgkin's lymphoma due to partial immune recovery and an increase in non-AIDS-defining malignancies due to prolonged survival. Management of HIV-infected patients with cancer requires a multidisciplinary approach, involving both oncologists and HIV physicians to optimally manage both diseases and drug interactions between anticancer and anti-HIV drugs. The French CANCERVIH group presents here a review and an experience of managing non-AIDS malignancies in HIV-infected individuals.

Radiation therapy of the primary tumour and/or metastases of digestive metastatic cancers.

Metastatic gastrointestinal cancer is not an uncommon situation, especially for pancreatic, gastric, and colorectal cancers. In this setting, few data are available on the impact of the treatment of the primary tumour. Oligometastatic disease is associated with longer survival in comparison with more advanced disease. Metastasis-directed therapy, such as stereotactic body radiotherapy, seems related to better outcomes, but the level of evidence is low. In most tumour locations, prospective data are very scarce and inclusion in ongoing trials is strongly recommended.

Esophageal cancer - French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR).

INTRODUCTION: This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022. RESULTS: EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.

Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1ß treated human intervertebral disc cells.

INTRODUCTION: Increased levels of proinflammatory cytokines seem to play a pivotal role in the development of back pain in a subpopulation of patients with degenerative intervertebral disc (IVD) disease. As current treatment options are mostly limited to surgical interventions or conservative treatment, anti-inflammatory substances might offer a novel, more target-orientated therapeutic approach. Triptolide (TPL), a natural substance found in the Chinese medicinal herb Tripterygium wilfordii Hook, has been demonstrated to possess anti-inflammatory effects in various cells, but no studies exist so far for the IVD. Therefore, the aim of this study was to determine the effects of TPL on human IVD cells by analyzing changes in gene expression and underlying molecular mechanisms. MATERIALS AND METHODS: In order to investigate the anti-inflammatory, anabolic and anti-catabolic effect of TPL, dose-dependency experiments (n = 5) and time course experiments (n = 5) were performed on IL-1ß prestimulated human IVD cells and changes in gene expression of IL-6/-8, TNF-α, PGE2S, MMP1/2/3/13, aggrecan and collagen-I/-II were analyzed by real-time RT-PCR. The molecular mechanisms underlying the effects observed upon TPL treatment were investigated by analyzing involvement of Toll-like receptors TLR2/4 (real-time RT-PCR, n = 5), NF-κB, MAP kinases p38, ERK and JNK (immunoblotting and immunocytochemistry, n = 4) as well as RNA polymerase II (immunoblotting, n = 3). RESULTS: Results showed that 50 nM TPL exhibited an anti-inflammatory, anti-catabolic and anabolic effect on the mRNA level for IL-6/-8, PGE2S, MMP1/2/3/13, aggrecan, collagen-II and TLR2/4, with most pronounced changes after 18 h for proinflammatory cytokines and MMPs or 30 h for TLRs and matrix proteins. However, we also observed an up-regulation of TNF-α at higher concentrations. The effects of TPL did not seem to be mediated via an inhibition of NF-κB or a decrease of RNA polymerase II levels, but TPL influenced activity of MAP kinases p38 and ERK (but not JNK) and expression of TLR2/4. CONCLUSIONS: In conclusion, TPL may possess promising potential for the treatment of inflammation-related discogenic back pain in vitro, but its analgetic effect will need to be confirmed in an appropriate in vivo animal model.

Radiotherapy and CDK inhibitors: Opportunities and risks.

CDK4/6 inhibitors are nowadays commonly used in metastatic HR+/HER2- breast cancer. Herein, we report a literature review regarding the benefits and risks of their combination with radiotherapy. Numerous pre-clinical studies have indeed shown a potential synergistic effect of these treatments in combination with radiotherapy in various types of cancers. On the other hand, some retrospective clinical studies have reported increased acute toxicity in case of digestive or pulmonary irradiation; therefore, it is advisable to discontinue CDK4/6 inhibitors before starting irradiation. Several prospective clinical trials are currently ongoing to assess the feasibility of this combination.

[News in gastrointestinal radiotherapy: The esophageal cancer]. / Actualités en radiothérapie digestive : le cancer de l'œsophage.

Esophageal cancers continue to have a poor prognosis, even if this has improved over the past 25 years due to better management. Pre-operative chemotherapy with Paclitaxel-Carboplatin followed by adjuvant immunotherapy with Nivolumab represents a major advance in the management of locally advanced oesophageal cancer. Pre-operatively, chemo-radiotherapy can be performed in combination with FOLFOX or Paclitaxel-Carboplatin. Several trials are currently ongoing to evaluate the benefit of immunotherapy in non-operable cancers. In contrast, dose escalation in locally advanced non-operable tumors and the combination of pre-operative chemo-radiotherapy with trastuzumab have not been shown to be beneficial.

Radiation therapy of cutaneous cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of cutaneous cancers. The indications of radiotherapy for skin cancers are not clearly defined because of the lack of randomized trials or prospective studies. For basal cell carcinomas, radiotherapy frequently offers a good local control, but a randomized trial showed that surgery is more efficient and less toxic. Indications of radiotherapy are contra-indications of surgery for patients older than 60, non-sclerodermiform histology and located in non-sensitive areas. Adjuvant radiotherapy could be proposed to squamous cell carcinomas, in case of poor prognostic factors. Dose of 60 to 70Gy are usually required, and must be modulated to the size of the lesions. Adjuvant radiotherapy seems beneficial for desmoplastic melanomas but not for the other histological types. Prophylactic nodal irradiation (45 to 50Gy), for locally advanced tumors (massive nodal involvement), decreases the locoregional failure rate but do not increase survival. Adjuvant radio- therapy (50 to 56Gy) for Merkel cell carcinomas increases also the local control rate, as demonstrated by meta-analysis and a large epidemiological study. Nodal areas must be included, if there is no surgical exploration (sentinel lymph node dissection). Kaposi sarcomas are radiosensitive and could be treated with relatively low doses (24 to 30Gy). Also, cutaneous lymphomas are good indications for radiotherapy: B lymphomas are electively treated with limited fields. The role of total skin electron therapy for T-lymphomas is still discussed; but palliative radiotherapy is very efficient in case of cutaneous nodules.

Radiotherapy for cancers of the oesophagus, cardia and stomach.

We present the updated recommendations of the French society for radiation oncology on radiotherapy of oesophageal cancer. Oesophageal cancer still remains a malignant tumour with a poor prognosis. Surgery remains the standard treatment for localized cancers, regardless of histology. For locally advanced stages, surgery remains a standard for adenocarcinomas after neoadjuvant treatment with chemotherapy or chemoradiotherapy. However, it is a therapeutic option after initial chemoradiotherapy for stage III squamous cell carcinomas, given the increased morbidity and mortality with a multimodal treatment, which results in an equivalent overall survival with or without surgery. Preoperative or exclusive chemoradiotherapy should be delivered according to validated regimens with an effective total dose (50Gy), if surgery is not planned or if the tumour is deemed resectable before chemoradiotherapy. Intensity-modulated radiotherapy significantly reduces irradiation of the lungs and heart and may reduce the morbidity of this treatment, especially in combination with surgery. In case of exclusive chemoradiotherapy, dose escalation beyond 50Gy is not currently recommended. Some technical considerations still remain questionable, such as the place of prophylactic lymph node irradiation, adaptive radiotherapy, evaluation of response during and after chemoradiotherapy and the value of proton therapy.

Tumour and normal tissue radiosensitivity.

The place of personalized treatments is highly increasing in medical and radiation oncology. During the last decades, a huge number of assays have been developed to predict responses of normal tissues and tumours. These tests have not yet been included into daily clinical practice but the recent developments of radiation oncology are paving the way of personalized strategies including the risk of tumour recurrence and normal tissue reactions. Concerning tumor radiosensitivity prediction, no test are currently used, even if the radiosensitivity index and the genome-based model for adjusting radiotherapy dose assays seem the most promising with level II of evidence. Commercial developments are under progress. Concerning normal tissue radiosensitivity prediction, single nucleotide polymorphims of prostate cancer patients and radiation-induced CD8 T-lymphocyte apoptosis breast and prostate assays are of level I of evidence. They can be proposed before the beginning of radiotherapy in order to propose personalized treatments according to both risks of tumour and normal tissue radiosensitivity. Commercial developments are also under way.

Role of radiotherapy for high risk localized prostate cancers.

Management of high-risk prostate cancers is still a subject of debate, because of the lack of randomized trial comparing surgery and radiotherapy. If external beam radiotherapy is proposed, it must be associated with a long-term androgen deprivation therapy, at least 18-months. Irradiation of pelvic lymph nodes seems to improve distant metastasis-free survival and is so indicated in most of the cases. Moderate hypofractionation is not validated for pelvic lymph nodes irradiation. A combination of external beam radiotherapy and brachytherapy improved biochemical control in randomized trials without impact on survival. But this combination has been evaluated in large retrospective studies and seems to improve specific and overall survivals. An integrated boost on the MRI-defined index lesion is another way of dose escalation and improved also biochemical control. Stereotactic radiotherapy is not a validated option at this moment. For each patient, according to the extension of the disease, age, comorbidities and also his willingness, the best approach must be chosen, ideally in multidisciplinary meeting.

[Place of radiotherapy in the treatment of cutaneous carcinomas]. / Place de la radiothérapie dans le traitement des carcinomes cutanés.

Basal cell carcinomas and cutaneous squamous cell carcinomas are among the most common cancerous tumors in the world. Their treatment is most often based on surgery. Adjuvant radiotherapy may be indicated in case of risk factors for recurrence or as an alternative to surgery if surgery is not feasible due to the patient's advanced age and/or co-morbidities or as an alternative to potentially mutilating surgery. Radiotherapy is also part of the therapeutic arsenal for rarer skin tumors such as Merkel cell carcinoma, cutaneous lymphomas, Kaposi's disease and cutaneous adnexal carcinomas.

[Gastric and pancreatic cancers: Will neoadjuvant (chemo)radiotherapy replace adjuvant chemoradiotherapy?] / Cancers gastriques et pancréatiques : la (chimio)radiothérapie néoadjuvante remplacera-t-elle la chimioradiothérapie adjuvante ?

For many years, adjuvant chemoradiotherapy remained essential in the therapeutic management of gastric and pancreatic adenocarcinomas. For these tumours, surgical excision, the only hope of offering the patient prolonged survival, is only possible in 20% of cases. The median survival of operated patients is only 12 to 20 months due to the frequency of locoregional and/or metastatic recurrences. For stomach cancers, adjuvant chemoradiotherapy is justified by the results of the phase III trial Intergroup 0116 published by MacDonald et al. The gain in survival was at the cost of significant toxicity. This treatment was supplanted in the early 2000s by perioperative chemotherapy. Currently, neoadjuvant chemoradiotherapy clinical studies are ongoing with the aim of improving treatments observance and tolerance. For pancreatic cancers, the role of adjuvant chemoradiotherapy has long been discussed because of trials with contradictory results. Neoadjuvant radiotherapy has many advantages in terms of efficacy and tolerance. It increases the chances of subsequent complete tumour resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal.

[Urological cancers of the elderly subject: the role of radiotherapy]. / Cancers urologiques du sujet âgé: rôle de la radiothérapie.

Urologic cancers are now usually found in elderly patients and the value of curative treatment is frequently asked. Life expectancy must not be underestimated with its consequence of undertreatment. Geriatric assessment is a good tool to make the right decision. For bladder and prostatic carcinomas, external beam radiation therapy is often the treatment of choice, if a curative option has been choose, because its toxicity is low in this population. In fact, many retrospectives studies have demonstrated that toxicity is equivalent in young and old patients. In prostate cancer, a recent randomised trial demonstrated that combination of irradiation and hormonal treatment increased biochemical control and overall survival over hormonal treatment alone. Hypofractionated schedules, more convenient to old patients, have been regularly reported for bladder cancers, but new techniques in radiation therapy seem to allow the use of this type of treatment schedules in prostate carcinomas.

Rationale for hypofractionation.

Fractionation was established more than fifty years ago as the best way to obtain a differential effect between tumors and normal tissues. However, new technologies allowed today to spare critical organs from the radiation fields. And so protracted courses of irradiation are no longer required. Hypofractionation have clear practical advantages over classical fractionation: it saves the patient time; it saves money for public health system; it reduces pressure on radiotherapy units. In several localization, it has proved to be as efficient as classical fractionation without increasing late effects. In prostate cancer, some radiobiological considerations argue in favor of a better efficiency, but clinical trials did not demonstrated differences in biological control. In conclusion, for all diseases where hypofractionation was demonstrated efficient, it must be fully implemented. Invoice procedures must be adapted to maintain a sufficient level of reimbursement of radiotherapy centers.

Combination of chemotherapy and radiotherapy: A thirty years evolution.

Chemoradiotherapy is now considered the standard of care for many locally advanced diseases. Cytotoxic drugs have been largely evaluated in this setting, with cisplatin and 5FU the most often used drugs. A large amount of pre-clinical studies has demonstrated the synergy between both modalities. Concomitant administration seems the more beneficial in many diseases. Emergence of new approaches, combining targeted therapies and radiotherapy (RT) is now a reality. The main example is the association of cetuximab and RT in head and neck carcinomas, even if, 14 years after the initial publication, the best way to use it is still unknown. New compounds as inhibitors of DNA-repair or immune checkpoints are under investigation and showed early promising results.

[Definitive or neo-adjuvant chemoradiation in esophageal carcinoma?] / Cancer de l'œsophage : radio-chimiothérapie exclusive ou préopératoire ?

Management of resectable esophageal carcinoma is based on a multimodal treatment associating neo-adjuvant chemoradiation before surgery. This therapeutic sequence allows a disease-free survival rate at 2 years around 45% but remains associated with a high post-operative morbidity. In case of definitive chemoradiotherapy, the dose delivered to the macroscopic disease is a controversial topic since decades and the prognosis of patients treated in this setting at the dose of 50Gy remains poor. This article proposes a review of the main published data and the ongoing studies related to the management of these patients.

[Follow-up after rectal cancer treatment]. / Surveillance après un cancer du rectum.

Along with the surgeon, the gastroenterologist and the general practitioner, the radiation oncologist is involved in the follow-up of patients with rectal cancer treated by radiation. Post-treatment follow-up is recommended by major professional expert groups and consists of clinical examination, monitoring of carcinoembryonic antigen, colonoscopy and computed tomography of the abdomen and pelvis. Three recent large phase III randomized trials demonstrated a lack of survival benefit from intensive follow-up strategies in comparison with minimal follow-up. However, a follow-up program is not only important for the detection of an early disease relapse but it can be also used for the identification and the management of long-term toxicity and sequalae related to rectal cancer treatment.

Early metabolic response to chemoradiotherapy by interim FDG PET/CT is associated with better overall survival and histological response in esophageal cancers.

BACKGROUND: Early assessment of response to neoadjuvant chemoradiotherapy (CRT) is crucial in determining the most suitable treatment strategy in locally advanced oesophageal cancer (LAEC). AIMS: We evaluated the impact of early metabolic response during CRT on overall survival (OS) and histological response. METHODS: Patients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment and during CRT after 20 Gy. RESULTS: 116 patients (Male: 66.4%, Median age: 63; squamous cell carcinomas (SCC): 70%) met inclusion criteria. Median OS was 21.7 months. There was a significant positive correlation between interim metabolic response and OS. In multivariate analysis, only metabolic response using the 50% cut-off value remained significantly associated with OS (IC95% = 0.28-0.73; p = 0.001). In this statistical analysis, surgery (p = 0.007) and T stage (p = 0.023) were also correlated with OS. There was a significant correlation between early metabolic response and local recurrence (Chi-squared test p = 0.0001). CONCLUSIONS: Early metabolic response using FDG PET/CT is associated with better OS, disease-free survival, local control and pathological response in patients treated by CRT for LAEC.

Salvage cryoablation for local recurrence of prostatic cancer after curative therapy.

PURPOSE: The purpose of this study was to determine the efficacy of salvage cryotherapy for intra-prostatic and local extraprostatic recurrences after curative treatment of prostate adenocarcinoma. MATERIAL AND METHOD: Twenty-eight men (mean age, 69±6 [SD] years; range: 51-82 years) treated with cryoablation for prostatic (N=21) or extraprostatic (N=7) recurrent prostate cancer after radiotherapy with or without associated prostatectomy were included. Technical success, complication and recurrences were reported. Biological recurrence was defined as an elevation ≥2ng/mL of prostate specific antigen (PSA) serum level after the treatment. RESULTS: The mean follow-up was 18 months. Among the 21 patients with intraprostatic recurrence, 14 had successful cryotherapy with a mean decrease in serum prostate-specific antigen (PSA) levels of -5.7±2.6 (SD) ng/mL (range: -2.1 to -16.9ng/mL). Four patients (19%) had early progression and three patients (14%) had delayed biological recurrence (mean time: 15 months). Among the 7 patients with extraprostatic recurrence, 2/7 (291%) had successful cryotherapy with a decrease in PSA serum level of -2.7±1.6 (SD) ng/mL (range: -0.5--5.5ng/mL) and 4/7 (57%) had early biological recurrence after cryotherapy that required androgen deprivation therapy, whereas 1/7 (4%) was lost to follow-up. No major complications were observed for both intra- and extraprostatic recurrence. CONCLUSION: Salvage cryoablation of locally recurrent prostate cancer after curative treatment is feasible and safe when the half prostate is treated. It could delay initiation of androgen deprivation therapy in these patients.