Avi Assouline

Radiation Therapy for Hypersalivation: A Prospective Study in 50 Amyotrophic Lateral Sclerosis Patients

PURPOSE This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. METHODS AND MATERIALS Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. RESULTS At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10(-6)). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (-77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. CONCLUSION Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition.

Merkel cell carcinoma of skin-current controversies and recommendations.

The review covers the current recommendations for Merkel cell carcinoma (MCC), with detailed discussion of many controversies. The 2010 AJCC staging system is more in-line with other skin malignancies although more complicated to use. The changes in staging system over time make comparison of studies difficult. A wide excision with margins of 2.5–3 cm is generally recommended. Even for primary </= 1 cm, there is a significant risk of nodal and distant metastases and hence sentinel node biopsy should be done if possible; otherwise adjuvant radiotherapy to the primary and nodal region should be given. Difficulties of setting up trials owing to the rarity of the disease and the mean age of the patient population result in infrequent reports of adjuvant or concurrent chemotherapy in the literature. The benefit, if any, is not great from published studies so far. However, there may be a subgroup of patients with high-risk features, e.g. node-positive and excellent performance status, for whom adjuvant or concurrent chemotherapy may be considered. Since local recurrence and metastases generally occur within 2 years of the initial diagnosis, patients should be followed more frequently in the first 2 years. However delayed recurrence can still occur in a small proportion of patients and long-term follow-up by a specialist is recommended provided that the general condition of the patient allows it. In summary, physician judgment in individual cases of MCC is advisable, to balance the risk of recurrence versus the complications of treatment.

Whole brain radiotherapy: prognostic factors and results of a radiation boost delivered through a conventional linear accelerator.

PURPOSE Assess prognostic factors for overall survival and the potential benefit of a boost in patients treated with whole brain radiation therapy (WBRT). METHODS AND MATERIALS From 2002 to 2006, a retrospective analysis was made from 250 unselected consecutive patients with secondary brain metastases from lung cancer, breast cancer and melanoma. Eighteen patients received surgery and were excluded from analysis. Four potential prognostic factors have been studied: primary tumor type, gender, number of metastases and improvement of neurological symptoms after radiation therapy. A subgroup analysis was performed to determine whether an additional boost could potentially improve outcome in patients who presented with less than three metastases, performance status <2, and no surgical resection of their metastasis. RESULTS Average follow-up was 10.3 months. Median overall survival was 5.6 months and survival rates at 1 and 2 years were 22.7% and 10%, respectively. Age less than 65 (p<0.01), neurological improvement after WBRT (p<0.01), and presence of less than three metastases were significant factors for overall survival in multivariate analysis. When focusing on the selected subgroup (120 assessable patients), median overall survival was 4.0 months in patients with no radiation boost, versus 8.9 months in patients with radiation boost (p=0.0024). CONCLUSIONS Survival and prognostic factors were similar to those found in the literature. Boost delivered after WBRT by a conventional particle accelerator could provide a benefit in selected patients, especially for centers that do not have radiotherapy techniques in stereotactic conditions. This warrants further prospective assessment.

Prophylactic Cranial Irradiation for Patients With Limited-Stage Small-Cell Lung Cancer With Response to Chemoradiation

BACKGROUND Previous clinical studies have generally reported that prophylactic cranial irradiation (PCI) was given to patients with a complete response (CR) to chemotherapy and chest radiotherapy in limited-stage small-cell lung cancer (SCLC). It is not clear if those with incomplete response (IR) would benefit from PCI. PATIENTS AND METHODS The Saskatchewan experience from 1981 through 2007 was reviewed. Patients were treated with chest radiotherapy and chemotherapy with or without PCI (typical doses: 2500 cGy in 10 fractions over 2 weeks, 3000 cGy in 15 fractions over 3 weeks, or 3000 cGy in 10 fractions over 2 weeks). RESULTS There were 289 patients treated for curative intent, 177/289 (61.2%) of whom received PCI. For the whole group of 289 patients, PCI resulted in significant overall survival (OS) and cause-specific survival (CSS) benefit (P = .0011 and 0.0005, respectively). The time to symptoms of first recurrence at any site with or without PCI was significantly different: 16.9 vs. 13.2 months (P = .0006). PCI significantly delayed the time to symptoms of first recurrence in the brain: 20.7 vs. 10.6 months (P < .0001). The first site of metastasis was the brain for 12.5% and 45.5% patients with CR with and without PCI, respectively (P = .02) and in 6.1% and 27.6% of patients with IR with and without PCI, respectively (P = .05). For the 93 patients with IR, PCI did not confer OS or CSS benefit (P = .32 and 0.39, respectively). CONCLUSIONS Patients with IR benefited from PCI, with a reduced rate of and a delayed time for the development of brain metastases, although without significant OS or CSS benefit. PCI could be considered for all patients with limited-stage SCLC responding to chemoradiation.

Reappraisal of clinical outcome in adult medulloblastomas with emphasis on patterns of relapse

Background. Clinical outcome and prognostic factors were assessed in adult medulloblastoma patients, with emphasis on patterns of relapse. Patients and methods. Records of 36 consecutive adult patients with medulloblastoma were reviewed. Patients were classified into 2 prognostic groups according to the extent of disease and quality of surgical excision based on the early postoperative magnetic resonance imaging (MRI) findings. Standard-risk (SR) patients (n = 11) received postoperative craniospinal radiation therapy (RT) only, 36 Gy, 1.8 Gy per daily fraction, with a 18 Gy boost to the posterior cerebral fossa (PCF). High-risk (HR) patients (n = 25) received additional adjuvant chemotherapy. Results. With a median follow-up of 46 months (range 5–155), 19 patients experienced tumour relapse. Sites of relapse(s) included tumour bed in 6 patients, resulting in a PCF control of 83.4%. Three-year overall survival (OS) and progression-free survival (PFS) were 67.3% and 57.4%, respectively. The comparison of the HR and SR populations demonstrated significant differences in OS (p = 0.005) and PFS (p = 0.001). Quality of surgical excision and extent of disease beyond the PCF were predictive factors for OS (p = 0.04, p = 0.001, respectively) and PFS (p = 0.004, and p = 0.02, respectively). Conclusion. The quality of resection was a significant prognostic factor, suggesting that surgery should be as extensive as possible. Systematic postoperative MRI allowed accurate selection of SR patients for whom RT alone was enough to obtain high local control. Every effort should be made to avoid RT disruption. Increased delay led to worse outcome.

Analysis of feasibility and toxicity of radiotherapy in centenarians.

nicate with people with dementia (85.4%); most employers will fire a 65-year-old employee with dementia (76.4%); individuals with dementia would not understand other people’s concern or worry (68.5%); individuals with dementia are impulsive and unpredictable (62.9%). These attitudes prevent the Chinese-American general public from encouraging older adults to seek early treatment and hinder public acceptance of individuals with dementia. Discrimination and shame can have a devastating effect on Chinese-Americans with dementia. Several areas of the lives of individuals with dementia would be affected, including employment and social relationships. Because community support is necessary for dementia treatment, participation of the general public remains crucial to overcoming the stigma of dementia, but lack of understanding of dementia in the Chinese community may contribute to social exclusion and discrimination toward individuals with dementia. An antistigma campaign, especially for Chinese-American immigrants, should focus on clarifying that people with dementia are neither dangerous nor unpredictable and that people with dementia are still functional, productive, and independent citizens in the Chinese-American community and on putting a human face (e.g., recruiting speakers with dementia) to inform the Chinese-American lay public that individuals with dementia understand other people’s concerns and worries. Future studies examining the relationship between knowledge about dementia and the shame associated with it in the Chinese American general public will better illustrate how to alleviate negative stereotyping of dementia. Because the media can play an important role in reaching out to this ethnic minority group, it is important to work on media interventions to prevent shame regarding dementia in the Chinese-American general public.

Radiotherapy among nonagenarians with anal or rectal carcinoma: should we avoid or adapt treatment?

© The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Dear editor, Radiotherapy is a cornerstone in the management of anal or rectal cancer. Because elderly patients are often excluded from clinical trials, little is known about radiotherapy’s therapeutic index (efficacy/toxicity ratio) in the geriatric population [1]. Still, the ageing of population imposes the challenge to treat older cancer patients and probably to adjust their treatment [2]. A few studies reported data on radiation-induced toxicities in nonagenarian patients, but data on efficacy are still scarce. For rectal cancer, preoperative radiotherapy programs were suggested to be feasible in elderly patients [3–5], with a preference for short protocols without chemotherapy [4]. For anal cancer, the safety of radiochemotherapy was only reported in limited sets of elderly patients [6]. The objective of the present study was to report efficacy and toxicity data on the radiotherapy treatment of nonagenarian patients with anal or rectal cancer. We analyzed the data of 34 nonagenarian patients with anal or rectal cancers: 27 (79.4%) with a rectal adenocarcinoma and 7 (20.6%) with an anal canal squamous cell carcinoma. At the time of irradiation treatment, the patients’ mean age was 92.7 years (standard deviation, 2.3 years). Before radiotherapy, 19 patients (55.9%) had an Eastern Cooperative Oncology Group Performance Status score of two or higher. Eleven patients (32.4%) were nursing home residents. Primarily, 16 patients (47.1%) were diagnosed with a locally advanced tumor (T3-4 or N1-3) and 6 (17.6%) with a metastatic disease. Seven patients (20.6%) underwent surgery before radiotherapy. Patient characteristics are shown in Table 1. Three-dimensional conformal radiotherapy was used for curative (n = 13, 38.2%) and palliative intents (n = 21, 61.8%). The median delivered dose was 43.5 Gy (range 6.0–64.0 Gy), and the median biologically equivalent dose in 2.0 Gy fractions (EQD2) was 44.7 Gyα/β=10 (range 8.0–64.0 Gyα/β=10). The median number of fractions was 14 (range 1–32), and the median dose was 3.0 Gy per fraction (range 1.8–10.0 Gy per fraction), with 13 patients (38.2%) receiving a dose less than 2.5 Gy per fraction. Median total treatment duration was 3.0 weeks (range 0.1–6.6 weeks). No concomitant chemotherapy was administered. In the entire cohort of 34 patients, 3 (8.8%) discontinued treatment: 2 because of patients’ noncompliance and 1 caused by an acute grade 3 toxicity. Eleven patients (32.3%) had a follow-up exceeding 6 months and were evaluated for late toxicity: 1 (2.9%) developed a grade 3–4 late fecal incontinence, 4 (11.8%) developed a grade 1–2 late toxicity (pelvic fibrosis, urinary incontinence, and fecal incontinence), and 6 (17.6%) did not report any late complication. Median follow-up time was 13.4 weeks (range 0–142.0 weeks), with a follow-up less than 4.0 weeks for 8 patients (23.5%). At the last follow-up, tumor control (defined as stable disease, partial response, and/or complete response) was achieved for 18 patients (52.9%), including 10 of the 13 patients treated in curative intent and 8 of the 21 patients treated with palliative intent; tumor-related symptoms were controlled in 13 patients (61.9%) who underwent a palliative radiotherapy. Nine patients (26.5%) had died at the last follow-up; of them, 8 (88.9%) had disease progression. In this study, we retrospectively assessed the safety and efficacy of radiotherapy for 34 nonagenarian patients with anal or rectal cancer. We observed only infrequent infield late toxicities (0% grade 5, 2.9% grade 3–4, and Open Access Chinese Journal of Cancer

Radiotherapy treatment of sialorrhea in patients with amyotrophic lateral sclerosis requiring non-invasive ventilation.

In amyotrophic lateral sclerosis (ALS), bulbar dysfunction may lead to sialorrhea [1], which affects up to 25 % of patients [2], and is a significant purveyor of distress trough a permanent drooling mouth, an increased risk of saliva aspiration pneumonia and a limited tolerance of non-invasive ventilation (NIV). We recently demonstrated that radiotherapy (RT) of the salivary glands was efficient and safe in the treatment of refractory sialorrhea in ALS [3]. Nevertheless, when orthopnoea occurs, decubitus position necessary to RT requires NIV. Performing RT in patients undergoing mechanical ventilation is technically challenging. The objective of this pilot study was to evaluate the efficacy and tolerance of a new protocol of RT specifically designed for ALS patients requiring mechanical ventilation for decubitus position. Five ALS patients, with established ALS according to revised El Escorial criteria [4], respiratory insufficiency and profuse sialorrhea resistant to classical pharmacological treatments (atropine drops, hyoscine patches and amitriptyline) were included. For patient characteristics see Table 1. All patients had severe orthopnea and were treated, at least over night, with non-invasive positive pressure ventilation without oxygen, using a facial mask. Irradiation was performed at the Clinique de la Porte de Saint-Cloud (Boulogne, France). Treatment was delivered through a conventional linear accelerator with 6 MV photons in both submandibular glands and two thirds of both parotid glands. Patients lied during sessions in 30 decubitus position for a maximum period of 10 min. The thermoplastic mask for radiotherapy was specifically designed to fit the facial mask of NIV, incorporating a large opening over the mouth and nose (Fig. 1). RT efficacy was assessed with the Sialorrhea Scoring Scale (SSS) that we previously validated in ALS patients [5]. The scale allows a semiquantification of sialorrhea in 9 grades ranging from 1 (dry mouth) to 9 (profuse sialorrhea). Approval for the study was obtained from the Regional Committee for Medical Research Ethics. Irradiation was completed in all 5 cases without any perprocedure complication. Assessment at the end of RT showed improvement in all patients with complete response (CR: SSS 1–3) in 4 cases and partial response (PR: SSS 4–5) in one case. Further evaluation at 3 months revealed persistent significant reduction in salivary production with 3 patients maintaining a CR and 2 patients a PR. Mild pain (acute toxicity of RT grade 1–2) was observed in 1 patient, but resolved in the weeks following the end of treatment. & Pierre-Francois Pradat pierre-francois.pradat@psl.aphp.fr

Male Breast Cancer Prognostic Factors Versus Female Counterparts with Propensity Scores and Matched-Pair Analysis

Objective: To assess the effect of prognostic factors and their impact on survival in male and female breast cancer. Methods: Medical records for men and women diagnosed with breast cancer referred to the cancer center for treatment were reviewed. Patients with distant metastatic diseases were excluded. Data on prognostic factors including age, nodal status, resection margin, use of hormonal therapy, chemotherapy with and without hormone and radiation therapy (RT), survival, and recurrence were analyzed. Survival estimates were obtained using Kaplan-Meier methodology. The Cox regression interaction was used to compare male and female differences in prognostic factors. Male breast cancer (MBC) and female breast cancer (FBC) were matched according to propensity scores and survival compared using Cox regression. Results: From 1963-2006, there were 75 MBC and 1,313 FBC totaling 1,388 breast cancers. The median age of the cohort was 53 (range: 23-90) years. Median follow-up was 90 (range: 0.4-339) months. Prognostic factors of patients were balanced among the groups after adjusting for propensity scores. A Cox model adjusting for propensity scores showed that overall survival (OS) (HR= 2.52 (1.65, 3.86), P<0.001) and distant disease recurrence-free survival (DDRFS) (HR= 2.39 (0.75, 3.04), P=0.003) were significantly different for MBC and FBC. Analyses that stratified by propensity score quintiles had similar findings: OS HR=2.41 (1.67, 3.47), P<0.001); DDRFS HR=2.89 (1.81, 4.60), P<0.001). When MBC and FBC were matched (1:3) by propensity scores, differences between MBC and FBC were again observed in OS (HR=1.94, 95%CI:1.18-3.19, P=0.009) and DDRFS (HR=2.79, 95%CI:1.36-5.75, P=0.005) with MBC at a higher risk of death and disease recurrence compared to FBC . Conclusion: This large series showed that MBC and FBC survivals are not similar, with MBC having a worse outcome. The finding of this study needs confirmation from a complete prospective database.

Focal 3D conformal high-dose hypofractionated radiotherapy for brain metastases

The optimal management of patients with few brain metastases is complex. On one hand, stereotactic radiation therapy is a keystone of treatment but is only applicable to highly selected patients fulfilling specific criteria who have access to an adequate radiation unit. On the other, whole-brain radiation therapy may improve survival, but deleterious effects on neurocognitive functions are well known. It has, however, been reported that selected subgroups of patients may benefit from focal dose escalation to brain metastases to prolong survival and the time to intracranial disease progression. Here, we discuss a clinical case to consider the interest of a focal high-dose hypofractionated radiation delivered through a conventional linear accelerator on a large brain metastasis for a patient with metastatic melanoma excluded for stereotactic radiotherapy.