Head and neck region consolidation radiotherapy and prophylactic cranial irradiation with hippocampal avoidance delivered with helical tomotherapy after induction chemotherapy for non-sinonasal neuroendocrine carcinoma of the upper airways

Background: Non-sinonasal neuroendocrine carcinomas (NSNECs) of the head and neck are considered an unfrequent clinico-pathological entity. Combined modality treatment represents an established therapeutic option for undifferentiated forms where distant metastasis is a common pattern of failure.Methods: We report on a case of NSNEC treated with sequential chemo-radiation consisting of 6 cycles of cisplatin and etoposide followed by loco-regional radiation to the head and neck and simultaneous prophylactic cranial irradiation to prevent from intracranial spread, delivered with helical tomotherapy with the 'hippocampal avoidance' technique in order to reduce neuro-cognitive late effects.Results: One year after the end of the whole combined modality approach, the patient achieved complete remission, with no treatment-related sub-acute and late effects.Conclusions: The present report highlights the importance of multidisciplinary management for NSNECs of the head and neck, as the possibility to achieve substantial cure rates with mild side effects with modern radiotherapy techniques. © 2012 Franco et al; BioMed Central Ltd

Inhibition of the inositol kinase Itpkb augments calcium signaling in lymphocytes and reveals a novel strategy to treat autoimmune disease

Emerging approaches to treat immune disorders target positive regulatory kinases downstream of antigen receptors with small molecule inhibitors. Here we provide evidence for an alternative approach in which inhibition of the negative regulatory inositol kinase Itpkb in mature T lymphocytes results in enhanced intracellular calcium levels following antigen receptor activation leading to T cell death. Using Itpkb conditional knockout mice and LMW Itpkb inhibitors these studies reveal that Itpkb through its product IP4 inhibits the Orai1/Stim1 calcium channel on lymphocytes. Pharmacological inhibition or genetic deletion of Itpkb results in elevated intracellular Ca2+ and induction of FasL and Bim resulting in T cell apoptosis. Deletion of Itpkb or treatment with Itpkb inhibitors blocks T-cell dependent antibody responses in vivo and prevents T cell driven arthritis in rats. These data identify Itpkb as an essential mediator of T cell activation and suggest Itpkb inhibition as a novel approach to treat autoimmune disease

The elderly at risk: aldosterone as modulator of the immune response to SARS-CoV-2 infection

The elderly population is the most susceptible to SARS-CoV-2 infection and develops the worst clinical phenotype with severe pneumonia and cardiac complications. Older COVID-19 patients are also at higher risk of sudden death, mainly attributable to electrolyte disorders and to an uncontrolled inflammatory response. After the identification of ACE 2 as the receptor of SARS-CoV-2 in human cells, several research studies have focused on the role of the activation of Renin Angiotensin System in COVID-19 clinical course. In the present opinion paper, we discuss the role of hyperaldosteronism in the increasing risk of cardiac complications in COVID-19 older patients. In particular, we focus on the immunoregulatory activity of aldosterone, as the last mediator of the Renin Angiotensin System cascade, in activating the innate and adaptive immune response related to SARS-CoV-2 infection in the elderly. Aldosterone may stimulate dendritic cells and the recruitment of monocytes/macrophages in the endothelium of coronary vessels, favoring the production of pro-inflammatory mediators and T-cells response. Higher basal levels of aldosterone together with SARS-CoV-2-induced production may explain the unfavorable course of COVID-19 in the elderly

The role of radiation therapy in vulvar cancer: Review of the current literature

The purpose of this article is to discuss the current role of radiation therapy in vulvar cancer and especially to review the recent literature relative to the use of intensity-modulated radiotherapy (IMRT) in disease management. Owing to the low incidence of vulvar cancer, at present there are no available results of cooperative prospective trials. As evidenced in dosimetric and preliminary retrospective clinical studies, the use of IMRT has resulted in superior normal tissue sparing and lower rates of acute and chronic toxicities compared to previous studies that used conventional approaches. Data on long-term outcomes in these patients remain limited

Accelerated hypofractionated adjuvant whole breast radiotherapy with concomitant photon boost after conserving surgery for early stage breast cancer: A prospective evaluation on 463 patients

The current standard therapeutic option for early stage breast cancer (EBC) employs a multimodality treatment approach including conservative surgery, radiotherapy, chemotherapy, and hormone therapy. The most common adjuvant radiotherapeutic strategy consists of external beam radiation therapy (EBRT) delivered to the whole breast using 1.8-2 Gy fractions given five times a week, up to a total dose of 45-50 Gy over a period of 5 weeks. In recent years, altered schedules employing larger dose per fraction delivered in fewer treatment sessions over a shorter overall treatment time began to be explored. We herein present clinical data on accelerated hypofractionated adjuvant whole-breast radiotherapy delivered on a daily basis for a total treatment time of 20 fractions. Between February 2005 and June 2009, a total of 463 patients underwent hypofractionated accelerated adjuvant radiation after conservative surgery for early breast cancer (pathological stage pTis, pT1 or pT2, pN0-N1). The basic course of radiotherapy consisted of 45 Gy, to the whole breast in 20 fractions with 2.25 Gy/fraction; an additional daily boost dose of 0.25 Gy was concomitantly delivered, to the lumpectomy cavity, for an additional total dose of 5 Gy. The cumulative nominal dose was 50 Gy. At follow-up, patients were examined at 3 and 6 months after the end of radiotherapy and twice a year afterward. Toxicity was scored according to the Common Terminology Criteria for Adverse Events, using the Radiation Therapy Oncology Group /European Organization for Research and Treatment of Cancer toxicity scale. Cosmetic results were assessed in agreement with the Harvard criteria. All the 463 patients treated with the accelerated hypofractionated adjuvant whole-breast radiotherapy schedule achieved at least 6 months' follow-up and subsequently were considered for the present analysis. With a median follow-up of 27 months, 5-year DFS is 93.1%. Only three patients experienced disease recurrence: two of them with an axillary nodal relapse; one patient with systemic spread. No local relapse occurred. No major toxicities (grade 3 or more) were detected during follow-up. Only 2% of the patients experienced grade 3 skin toxicity at the very end of the radiotherapy course. Cosmetic result was assessed and scored at 6 months, 1 year, 2 years: 100% of patients showed excellent or good cosmetic result. The explored accelerated hypofractionated adjuvant radiotherapeutic approach for early breast cancer with concomitant photon boost seems to be feasible providing consistent clinical results with excellent short-to-medium-term toxicity profile. © 2011 Wiley Periodicals, Inc

Hypofractionated whole-breast radiotherapy and concomitant boost after breast conservation in elderly patients

Aims: To report the 5- and 10-year results of accelerated hypofractionated whole-breast radiotherapy (WBRT) with concomitant boost to the tumor bed in 83 consecutive patients with early breast cancer aged >70 years. Methods: All patients were treated with breast conservation and hypofractionated WBRT. The prescription dose to the whole breast was 45 Gy (2.25 Gy/20 fractions) with an additional daily concomitant boost of 0.25 Gy to the surgical cavity (2.5 Gy/20 fractions up to 50 Gy). The maximum detected toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. We considered as skin toxicity: erythema, edema, desquamation, ulceration, hemorrhage, necrosis, telangiectasia, fibrosis-induration, hyperpigmentation, retraction and atrophy. Cosmetic results were assessed as set by the Harvard criteria. Results: With a median follow-up of 60 months (range 36-88), no local recurrence was observed. The maximum detected acute skin toxicity was G0 in 57% of patients, G1 in 40% and G2 in 3%. Late skin and subcutaneous toxicity was generally mild with no ≥G3 events. The cosmetic results were excellent in 69% of patients, good in 22%, fair in 5%, and poor in 4%. Conclusions: The present results support the use of hypofractionation employing a concomitant boost to the lumpectomy cavity in women aged >70 years. This is a convenient treatment option for both this type of population and health-care providers

Image-guided intensity-modulated radiotherapy for prostate cancer employing hypofractionation and simultaneous integrated boost: Results of a consecutive case series with focus on erectile function

Aim: To report on clinical outcomes of prostate cancer patients treated with hypofrationated radiotherapy employing a simultaneous integrated boost strategy. Patients and Methods: A consecutive series of 104 patients affected with prostate cancer was treated with intensity-modulated radiotherapy using a hypofractionated schedule and a simultaneous integrated boost consisting of 70 Gy (2.5 Gy daily) to the prostate gland, 63 Gy to the seminal vescicles (2.25 Gy daily) and 53.2 Gy to the pelvic nodes (1.9 Gy daily) when needed, delivered in 28 fractions. All patients underwent image-guided radiotherapy procedure consisting of daily cone-beam computed tomography. Results: After a median observation time of 26 (range=15-48) months, the 3-year biochemical failure-free survival was 96.5% [95% confidence interval (CI)=89%-98%], 3-year cancer-specific survival was 98.5% (95% CI=91%-99%) and 3-year overall survival was 96.5% (95% CI=89%-98%). The gastrointestinal and genitourinary toxicity profiles were mild with fewer than 2% of grade 3 events. Erectile function was partially affected by radiation in men potent at baseline. Conclusion: Hypofractionation delivered with intensity-modulated radiotherapy and a simultaneous integrated boost approach proved to be a safe and effective treatment option for patients with prostate cancer. Patients with a preserved baseline erectile function experience a decrease in functionality correlated with the mean dose received by penile bulb

Moderately hypofractionated radiotherapy with simultaneous integrated boost in prostate cancer: A comparative study with conventionally fractionated radiation

Background. To report 5-year clinical outcomes and toxicity in organ-confined prostate cancer (PCa) for low- and intermediate-risk patients treated with a moderately hypofractionated schedule of radiotherapy (RT) delivered with simultaneous integrated boost (SIB) compared to a conventionally fractionated RT regimen. Methods. Data of 384 patients with PCa treated between August 2006 and June 2017 were retrospectively reviewed. The treatment schedule consisted of hypofractionated RT (HYPO FR) with SIB up to 70 Gy to the prostate gland and 63 Gy to seminal vesicles delivered in 28 fractions or in conventionally fractionated RT (CONV FR) up to a total dose of 80 Gy in 40 fractions. Patient allocation to treatment was based on the time period considered. For intermediate-risk patients, androgen deprivation was given for a median duration of 6 months. The 5-year biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), and overall survival (OS) were assessed. Furthermore, we evaluated gastrointestinal (GI) and genitourinary (GU) toxicities. Uni- and multivariate Cox regression analyses were used to test the impact of clinical variables on both outcome and toxicity. Results. A total of 198 patients was treated with hypofractionated RT and 186 with the conventional schedule. At a median follow-up of 5 years, no significant differences were observed in terms of GI toxicity and outcome between the two groups. Early GU toxicity was significantly increased in HYPO FR, while late GU toxicity was significantly higher in CONV FR. In HYPO FR, a biochemical relapse occurred in 12 patients (6.1%), and 9 patients (4.5%) reported a clinical relapse (4 local, 2 locoregional, and 3 systemic recurrence). In CONV FR, 15 patients (8.1%) experienced a biochemical relapse and 11 patients (5.9%) showed a clinical relapse (5 local, 4 locoregional, and 3 systemic recurrences). Early grades 1-2 GU and GI toxicities were observed in 60 (30.3%) and 37 (18.7%) patients, respectively, in the hypofractionated group and in 33 (17.7%) and 27 (14.5%) patients, respectively, in the conventionally fractionated RT group. Late GU and GI toxicities occurred in 1 (0.51%) and 8 (4.1%) patients, respectively, in HYPO FR. In CONV FR, 5 (2.7%) and 6 (3.2%) patients experienced late GU and GI toxicities, respectively. The 5-year OS, bRFS, and CSS were 98.9%, 94.1%, and 99.5%, respectively, in HYPO FR, and 94.5%, 92.1%, and 99.0%, respectively, in CONV FR. Conclusions. Results obtained in this study showed that moderately hypofractionated RT employing SIB can be an effective approach providing valuable clinical outcomes with an acceptable toxicity profile