Local treatment in the setting of de novo metastatic rectal cancer: reappraisal of prognostic factors.

BACKGROUND: This retrospective study was conducted to: (1) provide more modern data on real-life local management of metastatic rectal cancer; (2) compare therapeutic strategies; and (3) identify prognostic factors of local failure, overall survival and progression-free survival. METHODS: Data about efficacy and acute toxicity were collected. Patients were diagnosed with metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. Local failure, overall survival and progression-free survival were correlated with patient, tumour and treatment characteristics using univariate and multivariate analyses. RESULTS: Data of 148 consecutive patients with metastatic rectal cancer were analysed. Median follow-up was 19 months. Median overall survival was 16 months. All patients received local radiotherapy, with a median equivalent 2 Gy per fraction dose of 47.7 Gy. Rectal surgery was performed in 97 patients (65.6%). The majority of patients (86/97, 88.7%) received pre-operative chemoradiation. In multivariate analysis, rectal surgery was found to be the only independent predictor of increased overall survival (24.6 vs 7.1 months, p <0.001). Of the patients undergoing surgical treatment, 22.8% presented with significant complications that required a delay of systemic treatment. Grade 3-4 acute radiation therapy-related toxicities were observed in 6.1% of patients, mainly gastrointestinal toxicities (5.4%). CONCLUSION: Rectal surgery was a key predictive factor of increased progression-free survival and overall survival in patients receiving at least local radiotherapy. In our series of real-life patients, local surgery and radiation seemed as well tolerated as reported in selected phase III non-metastatic rectal cancer patients. These data suggested that local management could be beneficial for metastatic rectal cancer patients.

Involvement of HIF-1α in the Detection, Signaling, and Repair of DNA Double-Strand Breaks after Photon and Carbon-Ion Irradiation.

Hypoxia-Inducible Factor 1α (HIF-1α), which promotes cancer cell survival, is the main regulator of oxygen homeostasis. Hypoxia combined with photon and carbon ion irradiation (C-ions) stabilizes HIF-1α. Silencing HIF-1α under hypoxia leads to substantial radiosensitization of Head-and-Neck Squamous Cell Carcinoma (HNSCC) cells after both photons and C-ions. Thus, this study aimed to clarify a potential involvement of HIF-1α in the detection, signaling, and repair of DNA Double-Strand-Breaks (DSBs) in response to both irradiations, in two HNSCC cell lines and their subpopulations of Cancer-Stem Cells (CSCs). After confirming the nucleoshuttling of HIF-1α in response to both exposure under hypoxia, we showed that silencing HIF-1α in non-CSCs and CSCs decreased the initiation of the DSB detection (P-ATM), and increased the residual phosphorylated H2AX (γH2AX) foci. While HIF-1α silencing did not modulate 53BP1 expression, P-DNA-PKcs (NHEJ-c) and RAD51 (HR) signals decreased. Altogether, our experiments demonstrate the involvement of HIF-1α in the detection and signaling of DSBs, but also in the main repair pathways (NHEJ-c and HR), without favoring one of them. Combining HIF-1α silencing with both types of radiation could therefore present a potential therapeutic benefit of targeting CSCs mostly present in tumor hypoxic niches.

Focus on the expected quality of reporting in SBRT/radiosurgery prospective studies: how far have we come in 30 years?

OBJECTIVES: We aimed at describing and assessing the quality of reporting in all published prospective trials about radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). METHODS: The Medline database was searched for. The reporting of study design, patients' and radiotherapy characteristics, previous and concurrent cancer treatments, acute and late toxicities and assessment of quality of life were collected. RESULTS: 114 articles - published between 1989 and 2019 - were analysed. 21 trials were randomised (18.4%). Randomisation information was unavailable in 59.6% of the publications. Data about randomisation, ITT analysis and whether the study was multicentre or not, had been significantly less reported during the 2010-2019 publication period than before (respectively 29.4% vs 57.4% (p < 0.001), 20.6% vs 57.4% (p < 0.001), 48.5% vs 68.1% (p < 0.001). 89.5% of the articles reported the number of included patients. Information about radiation total dose was available in 86% of cases and dose per fraction in 78.1%. Regarding the method of dose prescription, the prescription isodose was the most reported information (58.8%). The reporting of radiotherapy characteristics did not improve during the 2010 s-2019s. Acute and late high-grade toxicity was reported in 37.7 and 30.7%, respectively. Their reporting decreased in recent period, especially for all-grade late toxicities (p = 0.044). CONCLUSION: It seems necessary to meet stricter specifications to improve the quality of reporting. ADVANCES IN KNOWLEDGE: Our work results in one of the rare analyses of radiosurgery and SBRT publications. Literature must include necessary information to first, ensure treatments can be compared and reproduced and secondly, to permit to decide on new standards of care.

Combining radiation to EGFR and Bcl-2 blockade: a new approach to target cancer stem cells in head and neck squamous cell carcinoma.

PURPOSE: The clinical outcome of head and neck squamous cell carcinoma (HNSCC) remains poor, partly due to the presence of resistant cancer stem cells (CSCs) which are responsible of recurrences. CSCs have low EGFR expression and, conversely, overexpress the anti-apoptotic Bcl-2 protein, which is involved in resistance to apoptosis and the invasion/migration capacities of tumour cells. METHODS: The combination therapy of ABT-199, a Bcl-2 inhibitor, cetuximab an EGFR inhibitor, and radiation using an HNSCC model (SQ20B cell line) and its corresponding CSC subpopulation were evaluated in vitro (2D/3D cell proliferation; invasion/migration and apoptosis using videomicroscopy) and in vivo. RESULTS: Cetuximab strongly inhibited 2D and 3D cell proliferation, as well as invasion/migration, only in non-CSC-SQ20B cells, whereas ABT-199 selectively inhibited these mechanisms in SQ20B/CSCs. The combination of irradiation + cetuximab + ABT-199 increased the inhibition of the 2D and 3D cell proliferation, invasion/migration, and resistance to apoptosis in both cell sub-populations. In addition, in a nude mouse model with heterotopic tumour xenograft, a treatment combining cetuximab + ABT-199 with fractional irradiation strongly delayed the tumour growth and increased in vivo lifespan without side effects. CONCLUSION: Based on the present results, this triple combination therapy may represent a new opportunity for testing in clinical trials, particularly in locally advanced HNSCC.

Radiation-induced bystander and abscopal effects: important lessons from preclinical models.

Radiotherapy is a pivotal component in the curative treatment of patients with localised cancer and isolated metastasis, as well as being used as a palliative strategy for patients with disseminated disease. The clinical efficacy of radiotherapy has traditionally been attributed to the local effects of ionising radiation, which induces cell death by directly and indirectly inducing DNA damage, but substantial work has uncovered an unexpected and dual relationship between tumour irradiation and the host immune system. In clinical practice, it is, therefore, tempting to tailor immunotherapies with radiotherapy in order to synergise innate and adaptive immunity against cancer cells, as well as to bypass immune tolerance and exhaustion, with the aim of facilitating tumour regression. However, our understanding of how radiation impacts on immune system activation is still in its early stages, and concerns and challenges regarding therapeutic applications still need to be overcome. With the increasing use of immunotherapy and its common combination with ionising radiation, this review briefly delineates current knowledge about the non-targeted effects of radiotherapy, and aims to provide insights, at the preclinical level, into the mechanisms that are involved with the potential to yield clinically relevant combinatorial approaches of radiotherapy and immunotherapy.

CBCT evaluation of inter- and intra-fraction motions during prostate stereotactic body radiotherapy: a technical note.

BACKGROUND: In most clinical trials, gold fiducial markers are implanted in the prostate to tune the table position before each radiation beam. Yet, it is unclear if a cone-beam computed tomography (CBCT) should be performed before each beam to monitor a possible variation of the organs at risk (OARs) fullness, especially in case of recto-prostatic spacer implantation. The present study aimed at assessing the inter- and intra-fraction movements of prostate, bladder and rectum in patients implanted with a hyaluronic acid spacer and undergoing prostate stereotactic body radiotherapy (SBRT). METHODS: Data about consecutive patients undergoing prostate SBRT were prospectively collected between 2015 and 2019. Inter-and intra-fraction prostate displacements and volume variation of organs at risk (OARs) were assessed with CBCTs. RESULTS: Eight patients were included. They underwent prostate SBRT (37.5Gy, 5 fractions of 7.5Gy) guided by prostate gold fiducial markers. Inter-fraction variation of the bladder volume was insignificant. Intra-fraction mean increase of the bladder volume was modest (29 cc) but significant (p < 0.001). Both inter- and intra-fraction variations of the rectum volume were insignificant but for one patient. He had no rectal toxicity. The magnitude of table displacement necessary to match the prostate gold fiducial marker frequently exceeded the CTV/PTV margins (0.4 cm) before the first (35%) and the second arc (15%). Inter- and intra-fraction bladder and rectum volume variations did not correlate with prostate displacement. CONCLUSION: Major prostate position variations were reported. In-room kV fiducial imaging before each arc seems mandatory. Intra-fraction imaging of the OARs appears unnecessary. We suggest that only one CBCT is needed before the first arc. TRIAL REGISTRATION: NCT02361515, February 11th, 2015.

Persistent High-Risk HPV Infection and Molecular Changes Related to the Development of Cervical Cancer.

This article is a preliminary investigational study that is aimed at giving hints about the interesting biomarkers involved in the transition process from low-grade cervix lesion to invasive cervical cancer. Our study focuses on the risk factors and tumour molecular changes in one patient. First in 1986, she was diagnosed a preinvasive cervix lesion. Then, 16 years later, she was diagnosed an invasive cervical cancer. The 2002 diagnosis was a squamous cell carcinoma of the cervix, stage IIIB (FIGO), whereas in 1986, she had been diagnosed a high-grade squamous intraepithelial cervical lesion. Retrospectively, the analysis of samples of preneoplastic lesions and invasive cervical cancer confirmed the histopathological diagnoses and detected the presence of HPV type and HPV-16 variants, as well as the overexpression of proteins such as hTERT, IGF1Rα, IGF1Rß, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1Rα, IGF1Rß, CAIX, and GLUT1 variations seemed confirmed in the development and progression of cervical cancer. As a result, analyzing the molecular changes in one and same tumour that progresses from a low-grade cervix lesion to invasive cervical cancer could provide valuable information in order to improve detection, diagnosis, and treatment in the future.

[Stereotactic body radiotherapy: Passing fad or revolution?] / Radiothérapie stéréotaxique : changement de monde ou effet de mode ?

Stereotactic body radiotherapy (SBRT) is a young technology that can deliver a high dose of radiation to the target, utilizing either a single dose or a small number of fractions with a high degree of precision within the body. Various technical solutions co-exist nowadays, with particular features, possibilities and limitations. Health care authorities have currently validated SBRT in a very limited number of locations, but many indications are still under investigation. It is therefore challenging to accurately appreciate the SBRT therapeutic index, its place and its role within the anticancer therapeutic arsenal. The aim of the present review is to provide SBRT definitions, current indications, and summarize the future ways of research. There are three validated indications for SBRT: un-resecable T1-T2 non small cell lung cancer, <3 slow-growing pulmonary metastases secondary to a stabilized primary, and the tumours located close to the medulla. In other situations, the benefit of SBRT is still to be demonstrated. One of the most promising way of research is the ablative treatment of oligo metastatic cancers, with recent studies suggesting a survival benefit. Furthermore, the most recent data suggest that SBRT is safe. Finally, the SBRT combined with immune therapies is promising, since it could theoretically trigger the adaptative anticancer response.

[Radiotherapy and immune suppression: A short review]. / Radiothérapie et immunosuppression : synthèse de la littérature.

The management of patients undergoing immunosuppressive agents is really challenging. Based on precaution principle, it seems mandatory to stop immunosuppressive (or immunomodulating) agents during radiation. Yet, it is impossible in grafted patients. It is possible in patients with autoimmune disease, but in this case, the autoimmune disease might modify patient's radio-sensitivity. We provide a short review about the safety of radiotherapy in grafted/auto-immune patients. The literature is limited with data coming from outdated case-report or case-control studies. It seems that radiotherapy is feasible in grafted patients, but special dose-constraints limitations must probably be considered for the transplant and the other organs at risk. There is very little data about the safety of radiotherapy, when associated with immunomodulating agents. The most studied drug is the methotrexate but only its prescription as a chemotherapy (high doses for a short period of time) was reported. When used as an immunomodulator, it should probably be stopped 4 months before and after radiation. Apart from rheumatoid arthritis, it seems that collagen vascular diseases and especially systemic scleroderma and systemic lupus erythematous feature increased radio-sensitivity with increased severe late toxicities. Transplanted patients and collagen vascular disease patients should be informed that there is very little data about safety of radiation in their case.

Special Focus on Stage IV Cervical Cancer Patients: A Decade Experience.

OBJECTIVES: The aim of this study was to identify and compare prognostic factors, management strategies, and outcomes of very locally advanced cervical cancer (CC) (i.e., stage IVA) and metastatic CC (i.e., stage IVB). METHOD: A retrospective review was conducted based on all consecutive patients treatedfor stage IV CC in a comprehensive cancer care centre between 2004 and 2017. RESULTS: Sixty-eight patients were included. Performance status (PS) was ≥2 for 35.9%. Median age at diagnosis was 60.5. There were 24 stage IVA CC (35.3%) and 44 stage IVB CC (64.7%). Seventeen patients with stage IVB CC had only para-aortic lymph node metastases (38.6%), 13 had only distant metastases (29.5%), and 14 had both (31.8%). Patients with stage IVA CC experienced a radiotherapy with curative intent (n = 14, 58.3%) +/- concomitant chemotherapy, or a palliative treatment (n = 10, 41.7%). Twenty-three patients with stage IVB CC received a prior chemotherapy (52.3%), 11 a primary concomitant chemoradiation (25%), and 10 a palliative treatment (22.7%). The mean follow-up was 18.0 months. The 5-year overall survival was 5.1% for stage IVA (95% CI = 0.7-33.9), and 10.5% for stage IVB (95% CI = 3.7-29.7). In multivariate analysis, PS >1 was identified as a poor prognostic factor of disease-specific survival for stage IVA CC. PS >1 and pelvic lymph node involvement were identified as poor prognostic factors of overall survival and disease-specific survival for stage IVB CC. CONCLUSIONS: In daily clinical practice, outcomes of stages IV CC are poor. Treatment of advanced and metastatic CC remains challenging. New management strategies are needed, as well as efficient preventive strategies.

Quality insurance in head and neck cancer multidisciplinary team meetings: A watchful eye on real-life experience.

INTRODUCTION: Although Multidisciplinary Team Management (MDT) is integrated in most international head and neck cancer treatment guidelines, its applications and proceedings were rarely described. The present study explores a 6-year real-life experience in a French Comprehensive Cancer Care Center. METHODS: Patients, tumor and meeting characteristics of all consecutive cases discussed in head and neck MDT meetings between 2010 and 2015 were retrospectively reviewed. RESULTS: From 2010 to 2015, 1849 cases (accounting for 1786 patients) were discussed in 138 MDT meetings. Median age was 62 (range: 15-96). When reported (n = 310, 16.8%), performance status was ≥2 in 36.1% of patients. Tumors were mainly squamous cell carcinomas (n = 1664, 91.5%) of the larynx/hypo-pharynx (n = 630, 34.4%), oropharynx (n = 518; 28.3%) and oral cavity (n = 339; 18.5%). Tumors were diagnosed at a locally (n = 358, 25%), locally advanced (n = 946, 66%) or metastatic setting (n = 53, 3.7%). Mean number of discussed patients per MDT meeting was 16 (range: 3-32). Most patients were discussed once (n = 1663, 97%). Most patients (n = 969, 52%) underwent treatment before MDT meetings: mainly surgery (n = 709, 73.2%). The mean time between MDT meeting and first radiation course was 21 days (range: 1-116). DISCUSSION: Optimal multimodal treatment management is based on MDT meetings and results from the interaction and coordination of surgeons, medical and radiation oncologists. In the present series, most patients were discussed once despite the number of expected recurrences, suggesting that the management of tumor progression was not discussed in head and neck MDT meetings. Furthermore, most patients had surgery before MDT meeting, pointing out that MDT role and place still needs to be improved. Finally, the present population significantly differed from patients included in phase III clinical trials, with more advanced age and poorer condition. It calls for the necessity of a high-quality head and neck MDT meeting since evidence-based recommendations should be adapted to patient's frailties.

[Innovation in radiotherapy: A glance at 2018]. / Innovations en radiothérapie : un regard sur 2018.

Innovation in radiotherapy should meet multiple challenges, both technically, biologically, clinically and socially. Scientific, technological and biological advances have resulted in major changes in the implementation, indications, and therapeutic index of radiotherapy over the last century. Based on technical innovations (conformal radiotherapy, intensity modulation, CBCT, stereotactic body radiotherapy and MRI embedded system) and knowledge in cancer biology ("oxygen effect", "checkpoints", targeted therapies, molecular profiles and immunotherapy) highlighted in recent decades, the news in radiotherapy is rich and varied. The 2018 news are particularly focused in the role of hypofractionation in prostate cancer, the use of stereotactic body radiotherapy in oligometastatic patients, the possibility of de-intensify treatment in HPV-related oropharynx cancer, and the combination of short-term androgen deprivation to prostate bed salvage radiotherapy. The present manuscript reviews the 2018 latest advances.

Prevalence and outcome of patients referred for chest pain with high-sensitivity troponin elevation and no diagnosis at discharge.

INTRODUCTION: Specialized chest pain units appear to increase the proportion of patients with acute chest pain who are properly evaluated, but some of them remain doubtful. HYPOTHESIS: The aim of this study was to evaluate the survival and occurrence of cardiovascular events in patients without diagnosis at the end of management of chest pain with high-sensitivity troponin (Tn) elevation. METHOD: All consecutive patients who came to the cardiac emergency room of Poitiers University Hospital between January 1, 2014, and August 7, 2015, for chest pain and Tn elevation were included. The primary endpoint was the number of undiagnosed patients; secondary endpoints included survival and major adverse cardiac events. RESULTS: A total of 1001 patients (695 male; mean age, 68 ±16 years) who had chest pain and Tn elevation were included. Median follow-up was 24.5 (IQR, 14.7-29.5) months. Forty-seven (4.7%) patients remained without diagnosis. Compared with patients with diagnosis, these patients were younger (53.6 ±19.7 years; P < 0.0001) and had less hypertension (29.8%; P < 0.0001), diabetes (4.3%; P = 0.0016), and history of coronary artery disease (6.4%; P < 0.0001). No patients died or experienced MACE in 6-month follow-up. Survival curves showed the probability of survival was excellent, not only at 6 months, but also at 36 months (P = 0.0025). CONCLUSIONS: Less than 5% of patients referred for chest pain and with high-sensitivity Tn elevation remained without diagnosis after adapted care in the chest pain unit. Their 6-month prognosis was excellent.

Radiotherapy of rectal cancer in elderly patients: Real-world data assessment in a decade.

BACKGROUND AND PURPOSE: There is paucity of data on the efficacy and toxicity of radiotherapy in rectal cancer (RC) elderly patients. The objective was to identify management strategies and resulting outcomes in RC patients ≥70 years undergoing radiotherapy. MATERIAL AND METHODS: A retrospective study included consecutive RC patients ≥70 years undergoing rectal radiotherapy. RESULTS: From 2004-2015, 340 RC patients underwent pre-operative (n = 238; 70%), post-operative (n = 41, 12%), or exclusive (n = 61, 18%) radiotherapy, with a median age of 78.5 years old (range: 70-96). Radiotherapy protocols were tailored, with 54 different radiotherapy programs (alteration of the total dose, and/or fractionation, and/or volume). Median follow-up was 27.1 months. Acute and late grade 3-4 radio-induced toxicities were reported in 3.5% and 0.9% of patients. Metastatic setting (OR = 6.60, CI95% 1.47-46.03, p = 0.02), exclusive radiotherapy (OR = 5.08, CI95% 1.48-18.21, p = 0.009), and intensity-modulated radiotherapy (OR = 6.42, CI95% 1.31-24.73, p = 0.01) were associated with grade ≥3 acute toxicities in univariate analysis. Exclusive radiotherapy (OR = 9.79, CI95% 2.49-43.18, p = 0.001) and intensity-modulated radiotherapy (OR = 12.62, CI95% 2.05-71.26, p = 0.003) were independent predictive factors of grade ≥3 acute toxicities in multivariate analysis. A complete pathological response was achieved in 12 out of 221 pre-operative patients (5.4%). Age, tumor stage, and surgery were independent predictive factors of survival in multivariate analysis. At end of follow-up, 7.1% of patients experienced local relapse. CONCLUSION: Radiotherapy for RC in elderly patients appeared safe and manageable, perhaps due to the tailoring of radiotherapy protocols. Tailored management resulted in acceptable rate of local tumor control.

Radiothérapie et immunothérapie.

RADIATION THERAPY AND IMMUNOTHERAPY: Nowadays, it is known and recognized that the immune system has a central place in the mechanisms of oncogenesis and the effectiveness of anti-cancer therapies. The demonstration of the immuno-stimulatory ability of radiation therapy opens the field to new applications for this therapy already widely used in oncology area. Indeed, radiotherapy is capable of initiating and / or increasing the immune-mediated anti-tumor response. The combination of this "old" therapy with the "new" therapies that are immunotherapies then makes perfect sense. Although the potentiating effect of this combination is based on an interesting and well-documented biological rationale in preclinical data, there are still few clinical data available. The multiplication of trials, and the arrival of phase III trials should give us more perspective on the effectiveness and safety of this association. However, the lack of consensus concerning the optimization of these "immuno-radiotherapies" (characteristics of the tumor, irradiation regimen and treatment plan) could prove deleterious for the results of ongoing studies.

Pancarditis: an unusual complication of a group B streptococcal infection.

Pancarditis is a rare condition with a poor prognosis combining endocarditis, myocarditis with abscess formation, and purulent pericarditis. Diagnosis is often delayed and the clinical signs are predominantly those of the embolic complications. Literature is scarce. We present a unique and rare case of pancarditis, complicating a Streptococcal B infection in an immunocompetent, healthy, 54 year-old woman. The evolution was favourable under medical therapy alone and thanks to multimodality cardiac imaging diagnosis and follow-up.

Prognostic value of left atrial function in systemic light-chain amyloidosis: a cardiac magnetic resonance study.

BACKGROUND: Cardiac involvement in systemic light-chain amyloidosis (AL) imparts an adverse impact on outcome. The left atrium (LA), by virtue of its anatomical location and muscular wall, is commonly affected by the amyloid process. Although LA infiltration by amyloid fibrils leads to a reduction in its pump function, the infiltration of the left ventricular (LV) myocardium results in diastolic dysfunction with subsequent increase in filling pressures and LA enlargement. Even though left atrial volume (LAV) is an independent prognostic marker in many cardiomyopathies, its value in amyloid heart disease remains to be determined. In addition, few data are available as to the prognostic value of LA function in systemic AL. Using cardiac magnetic resonance (CMR), the current study aims to assess the prognostic significance of the maximal LAV and total LA emptying fraction (LAEF) in patients with AL. METHODS AND RESULTS: Fifty-four consecutive patients (age 66 ± 10 years, 59% males) with confirmed systemic AL and mean LV ejection fraction of 60 ± 12% underwent CMR. As compared with patients with no or minimal cardiac involvement (Mayo Clinic [MC] stage I), those at moderate and high risk (MC stages II and III) had significantly larger indexed maximal LAV (36 ± 15 vs. 46 ± 13 vs. 52 ± 19 mL/m(2), P = 0.03) and indexed minimal LAV (20 ± 6 vs. 34 ± 11 vs. 44 ± 17 mL/m(2), P < 0.001), lower LAEF (42 ± 9 vs. 26 ± 13 vs. 16 ± 9%, P < 0.0001) but similar LVEF. Furthermore, myocardial late gadolinium enhancement (LGE) was more frequent and significantly associated with lower LAEF. LAEF was also significantly lower in symptomatic (NHYA ≥ II, 22 ± 14%) as compared with asymptomatic patients (NYHA class I, 33 ± 13%, P = 0.006). Two-year survival rate was lower in patients with LAEF ≤ 16% as compared with those with LAEF > 16% (37 ± 11 vs. 94 ± 4%, P = 0.001). In multivariate analysis, lower LAEF remained independently associated with a higher risk of 2-year mortality (HR = 1.08 per 1% decrease, 95% CI: 1.02-1.15, P = 0.003). CONCLUSION: In patients with systemic AL, LAEF as assessed by CMR is associated with NYHA functional class, MC stage, myocardial LGE and 2-year mortality.

Intensity-modulated radiotherapy or volumetric-modulated arc therapy in patients with head and neck cancer: Focus on salivary glands dosimetry.

BACKGROUND: Despite radiotherapy (RT) technical improvements, high salivary dysfunction rates are still reported in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to report salivary glands dosimetry with volumetric-modulated arc therapy (VMAT) and intensity-modulated RT (IMRT). METHODS: Dosimetry of consecutive patients receiving IMRT or VMAT for proven HNSCC between 2007 and 2013 were retrospectively reviewed. RESULTS: Data of 609 patients were studied. Mean dose, mean maximum dose, and mean percentage of salivary gland volume receiving at least 26 Gy (V26) of the contralateral parotid were 24.50 Gy (range, 0-70.4 Gy), 39.08 Gy (range, 0.38-76.45 Gy), and 40.92% (range, 0% to 100%), respectively. Mean and maximum dose on contralateral submandibular gland were 48.18 Gy (range, 0.19-70.73 Gy), and 61.25 Gy (range, 0-75.8 Gy), respectively. CONCLUSION: Target volume coverage still has to be prioritized over organs at risk (OAR) sparing with new RT techniques. Submandibular glands are not sufficiently taken into account in guidelines. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1028-1034, 2016.

Radiotherapy for head and neck cancer in nonagenarian patients: a possible cornerstone?

In the field of radiotherapy, there is very little scientific data on the management of nonagenarians, especially in patients aged 90 years or more and with head and neck cancer (HNC). We made one of the first retrospective study of the feasibility and safety of radiotherapy in this population with HNC. Records of radiotherapy coming from four health facilities were studied to include all nonagenarian patients with HNC in the last 10 years and who received radiation therapy. We analyzed patient characteristics and primary cancers, as well as objective of the treatment (curative or palliative), efficacy and toxicity. Twenty patients receiving radiotherapy were identified; mean age was 93.2 years (standard deviation 2.8). Treatment was given with curative and palliative intent in 40 and 60 % of cases, respectively. The most common primary tumors were tumors of the salivary glands (30 % of cases), oral cavity tumors (25 % of cases) and thyroid tumors (15 % of cases). Median total prescribed dose was 47.5 Gy (12-70 Gy). Median number of delivered fractions was 18.5 (2-35 fractions). All patients received intensive supportive care during radiotherapy. Toxicities were mild to moderate. Radiotherapy could not be completed for four patients (20 % of cases). One patient developed grade 1-2 delayed toxicities. At the last follow-up, only four patients (20 % of cases) were alive. Cancer was cause of death in most cases. Radiotherapy may be performed for the nonagenarians with HNC. The total dose and fractionation must be adjusted to optimize the tolerance. However, the prognosis remains very poor, cancer being the main cause of death. Research of geriatric vulnerabilities prior to any treatment, in the context of a comprehensive geriatric assessment, is still recommended to select patients for radiotherapy.