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Purpose: To investigate the correlation between inflammatory-related parameters and overall survival (OS) and disease-free survival (DFS) in anal canal cancer population., Methods and Materials: Patients diagnosed with anal canal carcinoma and treated with curative intent chemoradiotherapy (CRT) were included. Data about pre-treatment complete blood count were collected. Neutrophil to lymphocyte ratio (NLR), fibrinogen (F), and a combination of these (F-NLR score) were correlated with OS., Results: A total of 58 patients were enrolled. In multivariate analysis, the strongest OS prognostic factor was NLR, with a hazard ratio (HR) for low NLR compared to high NLR of 1.30 (95% confidence interval 1.01-14.12). Kaplan-Meier survival analysis showed that patients with high NLR, F, and F-NLR had significantly shorter OS and DFS., Conclusion: To our knowledge, this is the first study providing evidence that elevated pre-treatment NLR, F, and F-NLR score significantly correlate with worse survival outcomes in patients with anal canal carcinoma. In view of our findings, future clinical trials in anal canal cancer patients are warranted to verify our results.

Purpose: To investigate the effects of the pretreatment neutrophil-to-lymphocyte ratio (N/L) on non-human papilloma virus (HPV)-related oropharyngeal cancer., Materials and Methods: N/L was calculated by dividing the neutrophil count by the lymphocyte count. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of N/L and other clinical factors on survival outcomes. High/low N/L groups were defined as > 4.7 and ≤4.7, respectively., Results: Data of 57 consecutive patients with non-HPV-related oropharyngeal cancer were analyzed. The 3-year disease-free survival was 79 versus 36.9% in favor of the low N/L group (p = 0.04). The 5-year overall survival was 71.6 versus 53.3% in the low N/L and high N/L group, respectively (p = 0.07)., Conclusion: N/L could play an important role in non-HPV-related oropharyngeal cancer progression and indicate prognosis., (© 2018 S. Karger AG, Basel.)

Firstly used in the early 90s to generate 3-dimensional projections of X-ray images, cone beam computed tomography (CBCT) has resulted in a large application in dentomaxillofacial imaging, even in children. CBCT uses ionizing radiation that may cause damage to the DNA, and children are at the greatest carcinogenesis risk due to their higher tissue radiosensitivity and their longer life expectancy compared to adults. The questions of whether the cancer risk is really increased after repeated dental CBCT in childhood and of what the underlying biological basis is have become hot topics in the field of dentistry and radiobiology. We performed an overview of the current literature to assess an acceptable role of CBCT in pediatric dentistry., (© 2019 S. Karger AG, Basel.)

To report the clinical results after definitive radiotherapy (RT) for indolent primary cutaneous B cell lymphoma (pcBCL). The data concerning all patients treated for indolent pcBCL with RT with a curative intent between 1992 and 2012 were reviewed. All cases were (re)classified according to the World Health Organization (WHO) guidelines. A total of 42 patients with biopsy-proven primary cutaneous follicle center lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL) were included. The median follow-up is 9.5 years. Treatment with RT resulted in complete response (CR) in all patients. Eight patients showed one or multiple relapses confined to the skin. No in-field recurrences were observed. For the entire cohort, the 10-year relapse-free survival (RFS) and overall survival (OS) were 71.1% and 87.1%, respectively. Univariate (UA) and multivariate (MA) analysis revealed extra-trunk primary lesion (MA) and multiple lesions (UA) as unfavorable prognostic factors. The 5-year RFS rate for patients with trunk lesion was 89.4% versus 66.9% for those with other location (p = 0.02). The 5-year RFS rates were 83.5 and 57.1% in case of single and multiple lesions (p = 0.04). An excellent survival can be achieved with definitive RT in indolent pcBCL. Patients with multiple and extra-trunk primary cutaneous lesions probably warrants intensification of therapy. Prospective studies are mandatory.

Background and Purpose: Complete surgical resection remains the only curative treatment option in locally advanced gastric cancer (GC). Several studies were conducted to prevent local recurrence and to increase the chance of cure. The aim of this study was to summarize our experience in locally advanced GC patients treated with adjuvant chemoradiotherapy (CRT) and to evaluate overall survival (OS), disease-free survival (DFS), toxicity rate and compliance to treatment., Materials and Methods: Locally advanced GC stage IB-III were included. Adjuvant CRT consisted of 45-50.4 Gy (1.8 Gy/day, 5 days/week) with concomitant Macdonald regimen (Mcd) or Epirubicin, Cisplatin and 5-Fluorouracil (ECF) scheme. Univariate and multivariate analysis of several prognostic factors for OS was conducted., Results: Fourty-nine GC patients were treated: 24 received Mcd and 25 received ECF. Median follow up was 48 months. Acute grade 3-4 toxicity was observed in 6 patients. The 2-year and 5-year OS rates were 65.3% and 41.5%, respectively. The 2-year and 5-year DFS were 59.2% and 41.2%, respectively. No prognostic factors were significantly associated with OS., Conclusions: Adjuvant CRT is a feasible strategy in locally advanced GC. It has an acceptable toxicity rate and it is able to increase both DFS and OS., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Background and Purpose: To report preliminary results of induction chemotherapy (IC) followed by neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer (LARC) patients., Materials and Methods: This is the preliminary evaluation of a phase II study. Patients with histologically proven rectal adenocarcinoma, stage II-III disease, who met the inclusion criteria, received induction FOLFOXIRI (5-FU, leucovorin, oxaliplatin and irinotecan) regimen in combination with targeted agents followed by CRT and surgery. Analysis of the first 8 patients was required to confirm the treatment feasibility before the accrual of 20 additional patients., Results: The first 8 patients were evaluated. The median follow-up time was 23 months. There were no treatment-related deaths. Trimodality strategy was well tolerated with high compliance and a good level of toxicity. There were no evidence of febrile neutropenia and any grade 4 adverse events were recorded. Three patients had pathologic complete response (pCR) and 1 patient had a nearly pCR (ypT1 ypN0)., Conclusion: Preliminary results are encouraging. FOLFOXIRI regimen plus targeted agents followed by CRT and surgery seems a safe approach. Longer follow-up and higher number of patients are mandatory to confirm such findings., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.

Purpose: Prostate cancer (PCa) cell radioresistance causes the failure of radiation therapy (RT) in localized or locally advanced disease. The aberrant accumulation of c-Myc oncoprotein, known to promote PCa onset and progression, may be due to the control of gene transcription and/or MEK/ERK-regulated protein stabilization. Here, we investigated the role of MEK/ERK signaling in PCa., Methods: LnCAP, 22Rv1, DU145, and PC3 PCa cell lines were used in in vitro and in vivo experiments. U0126, trametinib MEK/ERK inhibitors, and c-Myc shRNAs were used. Radiation was delivered using an x-6 MV photon linear accelerator. U0126 in vivo activity alone or in combination with irradiation was determined in murine xenografts., Results: Inhibition of MEK/ERK signaling down-regulated c-Myc protein in PCa cell lines to varying extents by affecting expression of RNA and protein, which in turn determined radiosensitization in in vitro and in vivo xenograft models of PCa cells. The crucial role played by c-Myc in the MEK/ERK pathways was demonstrated in 22Rv1 cells by the silencing of c-Myc by means of short hairpin mRNA, which yielded effects resembling the targeting of MEK/ERK signaling. The clinically approved compound trametinib used in vitro yielded the same effects as U0126 on growth and C-Myc expression. Notably, U0126 and trametinib induced a drastic down-regulation of BMX, which is known to prevent apoptosis in cancer cells., Conclusions: The results of our study suggest that signal transduction-based therapy can, by disrupting the MEK/ERK/c-Myc axis, reduce human PCa radioresistance caused by increased c-Myc expression in vivo and in vitro and restores apoptosis signals.

Renal cell carcinoma (RCC) is classically regarded as extremely resistant to classical fractionated radiation therapy (RT). Nowadays, there is convincing data supporting RCC radiosensitivity to high fraction doses, which may represent an ideal issue for new treatment strategies in primary and oligometastatic RCC disease. This review discusses the role of RT in RCC and its potential therapeutic scenario focusing on the most interesting clinical trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to develop nomograms for predicting the probability of overall survival (OS) and progression-free survival (PFS) in locally advanced cervical cancer treated with neoadjuvant chemotherapy and radical surgery., Materials and Methods: Nomograms to predict the 5-year OS rates and the 2-year PFS rates were constructed. Calibration plots were constructed, and concordance indices were calculated. Evaluated variableswere body mass index, age, tumor size, tumor histology, grading, lymphovascular space invasion, positive parametria, and positive lymph nodes., Results: In total 245 patients with locally advanced cervical cancer who underwent neoadjuvant chemotherapy and radical surgery were included for the construction of the nomogram. The 5-year OS and PFS were 72.6% and 66%, respectively. Tumor size, grading, and parametria status affected the rate of OS, whereas tumor size and positive parametria were the main independent PFS prognostic factors., Conclusion: We constructed a nomogram based on clinicopathological features in order to predict 2-year PFS and 5-year OS in locally advanced cervical cancer primarily treated with neoadjuvant chemotherapy followed by radical surgery. This tool might be particularly helpful for assisting in the follow-up of cervical cancer patients who have not undergone concurrent chemoradiotherapy.

Objective: Treatment of ovarian cancer (OC) is a challenge and its poor prognosis still remains a problem of major importance. Due to the lack of early and specific symptoms, the vast majority of women are diagnosed with an advanced stage disease. The aim of this meta-analysis is to evaluate the impact of OC screening program in asymptomatic women on clinical outcomes., Methods and Material: A systematic literature electronic search was conducted in Pubmed, Medline, Scopus, and ClinicalTrials.gov databases. Articles were selected with a systematic approach. Clinical trials concerning screening strategy compared with usual care in asymptomatic OC women were considered, without any restrictions on the publication date. Trials were eligible if participants were asymptomatic and postmenopausal women. Outcomes included OC diagnosis and disease specific mortality. The pooled relative risk (RR) was calculated using a fixed-effects model., Results: Overall, 3 randomized controlled trials met inclusion criteria, totaling 353,590 asymptomatic women. In total 177,188 women were assigned to screening program, and 176,402 women were assigned to usual care. The risk of OC diagnosis, both overall and at an early stage, was higher in screening group (RR = 1.07, 95% CI: 0.98-1.18; and RR = 1.30, 95% CI: 1.14-1.49, respectively). The RR for disease specific mortality was 0.96 (95% CI: 0.85-1.10)., Conclusion: Our results suggest the possible benefit of OC screening program in term of early stage diagnosis and reduced specific OC mortality. Further studies of environmental or constitutional factors may lead to the identification of patient populations that could benefit from a screening program., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: We report the treatment compliance, toxicity rates, and long-term clinical outcomes of elderly patients who received intensified neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC)., Patients and Methods: We identified a retrospective cohort of patients aged ≥ 70 years with LARC who received intensified neoadjuvant CRT, followed by surgery and adjuvant chemotherapy, from 2007 to 2014. Intensified neoadjuvant CRT consisted of radiotherapy (total dose, 50.4/54 Gy) with concomitant oxaliplatin (50 mg/m 2 /wk) and 5-fluorouracil (200 mg/m 2 in 5 daily continuous infusion)., Results: A total of 26 patients were included. All patients completed the programmed CRT. Severe acute toxicity was recorded in 19.2% of cases. Conservative surgery was performed in 16 patients, and a pathologic complete response was achieved in 19.2%. Overall, 26.9% of the patients died. The 5-year overall survival and disease-free survival rates were 70.6% and 65.5%, respectively., Conclusions: Intensified neoadjuvant CRT is an efficacious and safe treatment option for LARC in elderly patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In treating head and neck cancer (HNC), the objectives are provided for best functional results and minimal risk of serious complications. The choice of appropriate management depends primarily on specific site and stage of primary tumor at diagnosis. Radiation therapy (RT) with or without concomitant chemotherapy represents a classical treatment option. In this review, we provide an update of recent research strategies to counteract the existing damage caused by RT and highlight clinical trials currently in progress. We discuss the challenges in the evaluation of new stage system and RT-related toxicity onset. We mainly address the deficiencies and the advantages noted in the current treatment era., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to substantial improvement in the diagnosis and treatment of gynaecologic cancers, a better understanding of patient care needs to be revised. We reviewed the literature related to fertility preservation strategies in gynaecological cancer and discussed current general management approaches. New technical modalities and patients' own desire for motherhood should be integral and paramount in the clinical evaluation to significantly contribute to preserving fertility in those women diagnosed with gynaecologic cancers during the reproductive years.

Purpose: Bone metastases are a common cause of cancer-related pain. The aim of this study is to determine the optimal radiotherapy schedule for the treatment of painful bone metastases and verify if could cause different biological effects on bone. This has been achieved using functional Magnetic Resonance Imaging (MRI) with diffusion-weighted imaging (DWI)., Patients and Methods: Fifteen patients received Multiple Fractions Radiation Therapy (MFRT) with a total dose of 30Gy in 10 daily fractions of 3Gy given over 2 weeks and 15 patients received a Single Fraction Radiation Therapy (SFRT) with a dose of 8Gy. Quantitative Apparent Diffusion Coefficient (ADC) values after SFRT or MFRT were compared with response to treatment (pain relief), assessed by Visual Analogue Scale (VAS) before radiotherapy and at 1 and 3 months after the completion of treatment., Results: The two schedules had equal efficacy in terms of pain control, without any difference at 1 and 3 months post radiotherapy. In both treatments, pain reduction was related to an increase in the ADC. However, the median ADC value had an increase of 575 points between the baseline and 3 months (from 1010 to 1585, p=0.02) in the 30Gy group, while it was only 178 points (from 1417 to 1595) in the 8Gy group., Conclusions: The increase in the ADC values after radiotherapy corresponds to increased cell death. Despite an equal pain control, MFRT treatment seems to be more effective to achieve cancer cells kill. Our preliminary data could also explain the higher retreatment rates in SFRT vs MFRT in long survivors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Salivary gland malignant tumor (SGMT) is a malignant disease requiring multidisciplinary approach. The rare incidence and the consequent lack of robust evidence-based medicine has called for a comprehensive update to draw recommendations for clinical practice. This paper is a summary of the XXX Head and Neck Unit guidelines regarding the management of SGMT. Recommendations include the indications for exclusive and adjuvant therapy, as well as metastatic management, for both major and minor SGMT., (Copyright © 2017 Elsevier B.V. All rights reserved.)

To report long-term outcomes and toxicity rates after chemotherapy (CHT) followed by radiotherapy (RT) in the highly active antiretroviral therapy (HAART) era in human immunodeficiency virus (HIV) positive patients with head and neck diffuse large B cell lymphomas (HN-DLBCL). Clinical data concerning consecutive HIV patients treated for DLBCL located in head and neck region with CHT and RT were retrospectively reviewed. Systemic treatment consisted of combination CHT agents given with concomitant HAART and regimen was left to oncologists' discretion. Involved field RT was delivered at a total dose of 30-36 Gy (2 Gy per fraction). Survival rates were estimated using the Kaplan-Meier method. Toxicity was evaluated using National Cancer Institute's Common Terminology Criteria for Adverse Events. Overall, 13 patients were included. There were no missing data. Eight patients had advanced disease (stage III-IV = 8; 61.5%). The most common primary tumor location was oral cavity (n = 7) with large mass at presentation. All patients completed the programmed treatment. Severe acute toxicity was observed in one patient, only. Overall, three patients had died and no treatment-related deaths occurred. After a median follow-up of 152 months, the 20-year overall survival and disease-free survival rates were 65.9 and 41.5%, respectively. Globally, there were no RT-related late complications. This data analysis suggested that CHT followed by RT can be safety proposed in the management of patients with HIV-related HN-DLBCL in the HAART era. Further investigations are necessary to validate our results.

To compare adjuvant conventional radiotherapy (C-RT) to hypofractionated schedule (HF-RT) in early breast cancer. Between May 2012 and September 2015, 120 patients were included in the analysis. All patients underwent conservative surgery and adjuvant RT. RT was delivered in C-RT (50 Gy; 2 Gy/fr) or HF-RT (42.5 Gy; 2.66 Gy/fr), followed by a tumor bed boost (10 Gy; 2 Gy/fr). RT-induced toxicity was recorded and compared between groups. Toxicity results were graded according to the Common Terminology Criteria for Adverse Events guidelines. A multivariate analysis was performed of the factors associated with acute toxicity onset. Mild acute skin toxicity was observed in 71.7% of patients. No grade 4 toxicity was observed. From the multivariate analysis, Breast volume and RT fractionation significantly affected acute radiation-related toxicity. No increase in late toxic effects has been reported between C-RT and HF-RT schedules. Overall, the 2-year disease free survival was 94.4%. HF-RT represents a valid adjuvant treatment option in early breast cancer patients, without negative impact on acute and late radiation sequelae, as well as tumor control., (© 2017 Wiley Periodicals, Inc.)

Head neck cancer (HNC) is generally treated with a multimodality approach. Loco-regional-distant control is often worst, due to the advantage stage disease at diagnosis and the optimal treatment option remains an unresolved issue. Metronomic chemotherapy (MCHT) is an emerging therapeutic option in clinical oncology and it may prove useful in HNC patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Bone metastases represent an important complication of malignant tumours. Despite improvement in surgical techniques and advances in systemic therapies, management of patients with bone metastatic disease remains a powerful cornerstone for the radiation oncologist. The primary goal of radiation therapy is to provide pain relief, preserving patient's quality of life.

The field of prostate oncology has continued to change dramatically. It has truly become a field that is intensely linked to molecular genetic alterations, especially DNA-repair defects. Germline breast cancer 1 gene (BRCA1) and breast cancer 2 gene (BRCA2) mutations are implicated in the highest risk of prostate cancer (PC) predisposition and aggressiveness. Poly adenosine diphosphate ribose polymerase (PARP) proteins play a key role in DNA repair mechanisms and represent a valid target for new therapies. Olaparib is an oral PARP inhibitor that blocks DNA repair pathway and coupled with BRCA mutated-disease results in tumor cell death. In phase II clinical trials, including patients with advanced castration-resistant PC, olaparib seems to be efficacious and well tolerated. Waiting for randomized phase III trials, olaparib should be considered as a promising treatment option for PC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To determine the performance of texture analysis (TA), diffusion-weighted imaging, and perfusion MR (pMRI) in predicting tumoral response in patients treated with neoadjuvant chemoradiotherapy (CRT)., Methods: 12 consecutive patients (8 females, 4 males, 63.2 ± 13.4 years) with rectal cancer were prospectively enrolled, and underwent pre-treatment 3T MRI. Treatment protocol consisted of neoadjuvant CRT with oxaliplatin and 5-fluorouracile. Unenhanced T2-weighted images TA (kurtosis), apparent diffusion coefficient (ADC), and pMRI parameters (Ktrans, Kep, Ve, IAUGC) were quantified by manually delineating a region of interest around the tumor outline. After CRT, all patients underwent complete surgical resection and the surgical specimen served as the gold standard. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminatory power of each quantitative parameter to predict complete response., Results: Pathological complete response (pCR) was reported in six patients and partial response (PR) in three patients. Three patients were classified as non-responders (NR). Pre-treatment kurtosis was significantly lower in the pCR sub-group in comparison with PR + NR (p = .01). Among ADC and pMRI parameters, only Ve was significantly lower in the pCR sub-group compared with PR + NR (p = .01). A significant negative correlation between kurtosis and ADC (r = -0.650, p = .022) was observed. Pre-treatment area under the ROC curves (AUC), to discriminate between pCR and PR + NR, was significantly higher for kurtosis (0.861, p = .001) and Ve (0.861, p = .003) compared to all other parameters. The optimal cutoff value for pre-treatment kurtosis and Ve was ≤0.19 (100% sensitivity, 67% specificity) and ≤0.311 (83% sensitivity, 83% specificity), respectively., Conclusion: Pre-treatment kurtosis derived from T2w images and Ve from pMRI have the potential to act as imaging biomarkers of rectal cancer response to neoadjuvant CRT.

Aim: To compare gross tumor volume (GTV) definition in locally advanced head and neck squamous cell carcinoma (LAHNSCC) using diffusion-weighted magnetic resonance imaging (DW-MRI) and computed tomography (CT) with intravenous contrast., Patients and Methods: Patients with LAHNSCC were imaged with CT and DW-MRI before treatment. GTV was delineated in both CT and DW-MRI images by two investigators. CT and MRI images were co-registered and volume data were extracted for statistical analysis., Results: In general, DW-MRI volumes [based on the apparent diffusion coefficient (ADC)] were smaller than CT-based volumes. For all patients, GTV delineation based on pre-treatment DW-MRI was significantly smaller than that based on CT scan (CT-GTV) (p=0.0078). The mean difference (95% limits of agreement) between the two investigators was -0.37 cm(3) for CT-GTV and 0.17 cm(3) for ADC-GTV measurements, respectively., Conclusion: DW-MRI radiotherapy GTVs are smaller than CT-based targets with less interobserver variability. Further validation of these preliminary results is necessary in a much larger patient group., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: To report the long-term follow-up data and determine the toxicity rate concerning patients with locally advanced rectal cancer (LARC) treated with an intensified neoadjuvant treatment regimen., Patients and Methods: Patients with histologically proven stage II to III adenocarcinoma of the rectum were included and treated with a trimodal approach. Intensified neoadjuvant treatment (chemoradiotherapy [CRT]) consisted of radiotherapy (total dose 50.4/54 Gy) and concomitant oxaliplatin (50 mg/m(2)/week) and 5-fluorouracil (200 mg/m(2)/5 daily continuous infusion). Surgery was planned 7 to 9 weeks after the end of CRT. Adjuvant chemotherapy was recommended in those patients with lymph node metastasis at diagnosis., Results: One hundred patients (median age, 64 years) were eligible. Overall, the 5-year overall survival and disease-free survival (DFS) were 76.4% and 74.5%, respectively. CRT was well tolerated, with only 17% grade 3/4 acute toxicity. Twenty-four patients (24%) had a pathologic complete response (pCR), and only 1 patient had perioperative metastasis. The 5-year DFS were 95.7% and 66.7% for pCR and no-pCR tumor histology, respectively (P = .0275)., Conclusion: Although oxaliplatin is not considered to be a standard treatment, the high 5-year rate of overall survival and DFS, the low severe toxicity rates, and the effective benefit on pCR and perioperative metastasis support an intensified treatment regimen for LARC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Treatment strategy in squamous cell carcinoma (SCC) of the posterior pharyngeal wall is still being debated., Methods: We performed a retrospective analysis according to delivered treatment., Results: One hundred eighty patients were treated between 1997 and 2011. Eighty-nine patients (49.4%) received surgery +/- radiotherapy (RT), whereas 91 (50.6%) received definitive RT +/- chemoradiotherapy (RT/CRT). Five-year overall survival (OS) was 33.4%. There was a significant 5-year OS benefit in surgical treatment versus RT/CRT (43% vs 24.1%; p = .002). Multivariate analysis showed that current smokers, T3 to T4 classification, well-differentiated SCC, and nonsurgical treatment were associated with reduced OS. Subgroup analysis showed significant survival benefit of surgical treatment compared with RT/CRT in patients with T1 to T2 but not in T3 to T4 disease., Conclusion: Surgical management translated into a survival benefit, even in early T classification. These results should be interpreted with caution for selection bias. Surgery remains the standard of care in localized posterior pharyngeal wall SCC. Primary CRT should be considered for nonoperable disease. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1722-E1729., (© 2015 Wiley Periodicals, Inc.)

Background: The purpose of this study was to evaluate the tolerability of concurrent radiotherapy and cetuximab (bioradiotherapy [BRT]) after taxane-based induction chemotherapy in head and neck squamous cell carcinoma (HNSCC)., Methods: One hundred four patients with HNSCC received BRT with (29%) or without (71%) prior taxane-based induction chemotherapy., Results: Radiodermatitis (97%) and skin rash (65%) occurred frequently, but there was no difference of occurrence or the grade of the rash observed in the 2 populations. However, patients receiving taxane-based induction chemotherapy had a less severe rash as compared with patients without induction chemotherapy. Mucositis and dysphagia were frequent and comparable in the 2 groups. The occurrence of a skin rash (at any grade) did not predict an increased overall survival (OS) in the overall population, but it was associated with an improved 3-year OS in patients receiving taxane-based induction chemotherapy. OS was not influenced by the skin rash grade in the overall population of the 2 treatment subgroups., Conclusion: Taxane-based induction chemotherapy did not increase the rate of cetuximab-related toxicities. © 2015 Wiley Periodicals, Inc. Head Neck 38: E905-E910, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: To analyze the efficacy and toxicity of bevacizumab on survival outcomes in recurrent ovarian cancer., Results: Bevacizumab was associated with significant improvement of PFS and OS compared with standard treatment with HRs of 0.53 (95% CI 0.44 - 0.63; p < 0.00001) and 0.87 (95% CI, 0.77 to 0.99; p = 0.03), respectively.Bevacizumab increased the incidence of G3/G4 hypertension (RR 19.01, 95% CI 7.77 - 46.55; p < 0.00001), proteinuria (RR 17.31, 95% CI 5.42 - 55.25; p < 0.00001), arterial thromboembolic events (ATE) (RR 4.99, 95% CI 1.29 - 19.27; p = 0.02) and bleeding (RR 3.14, 95% CI 1.35 - 7.32; p = 0.008)., Materials and Methods: Three randomized phase III trials representing 1502 patients were identified.Pooled hazard ratio (HR), odd ratio (OR), risk ratio (RR) with 95% confidence interval (CI) were calculated using fixed or random effects model., Conclusions: Adding bevacizumab to standard chemotherapy improved ORR, PFS and OS, and it had a higher, but manageable, incidence of toxicities graded 3 to 4.

Background: Women with BRCA1 and BRCA2 mutations have substantially elevated risk of developing breast cancer. The aim of this study was to clarify the role of bilateral risk-reducing mastectomy (BRRM) in reducing breast cancer risk in women carriers of BRCA1 and BRCA2 mutations., Methods: The Pubmed, MEDLINE and Scopus databases were searched to retrieve articles written in the English language. Two investigators independently extracted the characteristics and results of the selected studies. Only prospective trials with available absolute numbers of breast cancer and death events were included. Pooled hazard ratio (HR) with 95 % confidence interval (CI) was calculated using fixed or random effects model., Results: Meta-analysis of four prospective studies, including 2635 patients, demonstrated a significant risk reduction of breast cancer incidence in BRCA1 and BRCA2 mutation carriers receiving BRRM (HR 0.07; 95 % CI 0.01-0.44; p = 0.004). Among patients without previous risk-reducing salpingo-oophorectomy, a significant benefit was similarly recorded (HR 0.06; 95 % CI 0.01-0.41; p = 0.005)., Conclusions: Performing BRRM may lead to highly significant risk reduction of breast cancer in BRCA1 and BRCA2 mutation carriers. These data allow clinicians to discuss more in-depth with patients all the available options in order to design better management strategies.

Rectal carcinoma represents the 30% of all colorectal cancers, with about 40000 new cases/years. In the past two decades, the management of rectal cancer has made important progress, highlighting the main role of a multimodality strategy approach, combining surgery, radiation therapy and chemotherapy. Nowadays, surgery remains the primary treatment and neo-adjuvant chemoradiotherapy, based on fluoropyrimidine (5-FU) continuous infusion, is considered the standard in locally advanced rectal carcinoma. The aim is to reduce the incidence of local recurrence and to perform a conservative surgery. To improve these purposes different drugs combination have been tested in the neo-adjuvant setting. At American Society of Clinical Oncology 2014 an important abstract was presented focusing on the role of adding oxaliplatin to concomitant treatment, in patients with locally advanced rectal carcinoma. Rodel et al reported on the CAO/ARO/AIO-04 randomized phase III trial that compared standard treatment with 5-FU and radiation therapy, to oxaliplatin plus 5-FU in association with radiation therapy. The addition of oxaliplatin to the neo-adjuvant treatment has been shown to improve disease-free survival from 71.2% to 75.9% (P = 0.03). This editorial was planned to clarify the optimal treatment in patients with locally advanced rectal cancer, considering the results from CAO/ARO/AIO-04 study.

Systemic neo-adjuvant therapy plays a primary role in the management of locally advanced breast cancer. Without having any negative effect in overall survival, induction chemotherapy potentially assures a surgery approach in unresectable disease or a conservative treatment in technically resectable disease and acts on a well-vascularized tumor bed, without the modifications induced by surgery. A specific issue has a central function in the neo-adjuvant setting: lymph nodes status. It still represents one of the strongest predictors of long-term prognosis in breast cancer. The discussion of regional radiation therapy should be a matter of debate, especially in a pathological complete response. Currently, the indication for radiotherapy is based on the clinical stage before the surgery, even for the irradiation of the loco-regional lymph nodes. Regardless of pathological down-staging, radiation therapy is accepted as standard adjuvant treatment in locally advanced breast cancer.

Brain metastases represent an important healthcare problem. Approximately 20%-40% of patients develop disease metastatic to the brain over the course of their cancer history. Palliative treatment of brain metastases requires for immediate control and, at least temporarily, a remission of the symptoms because many of the symptoms associated with brain metastases reduce the patient's quality of life. Radiation therapy is used to treat this clinical circumstance. The aim of this review is to assess the efficacy and the toxicity of radiotherapeutic treatment approaches and to provide treatment recommendation for brain metastases., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Pancreatoduodenectomy remains the recommended treatment in potentially curative strategies for pancreatic carcinoma. Due to high local failure rates even after complete resection, a multi-modality treatment approach is paramount in the management of resectable disease. Despite there being insufficient evidence to recommend a specific neoadjuvant strategy, several studies have tested the use of preoperative chemoradiotherapy in this sub-group of patients, achieving promising results. The treatment is well-tolerated, with higher rates of negative margins and lower rates of lymph node positivity at resection, a decrease in local failure and benefit in overall survival. Considering the poor oncological results after primary surgical treatment, neoadjuvant strategy should be considered as a valid alternative in resectable pancreatic carcinoma., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To compare toxicity profiles of two different intensity-modulated radiation therapy (IMRT) strategies in patients with high-risk prostate cancer., Patients and Methods: From May 2010 to September 2012, 43 patients with high-risk prostate cancer were treated with IMRT and concurrent hormone therapy; 23 patients were treated by conventional fractionation (IMRT/C) and 20 patients by simultaneous integrated boost (IMRT/SIB). Acute and late toxicities were compared for each group., Results: Severe acute genitourinary toxicity was recorded in 8.6% and 2% of patients in the IMRT/C and IMRT/SIB group, respectively. Genitourinary toxicity G2 was observed in 39.1% (IMRT/C group) and 25% (IMRT/SIB group) of patients. Severe acute gastrointestinal toxicity was not observed; Grade 2 acute gastrointestinal toxicity was recorded in 21.7% (IMRT/C group) and 10% (IMRT/SIB group). Grade 2 late genitourinary toxicity was observed in 26% (IMRT/C group) and 15% (IMRT/SIB group), whereas G2 late gastrointestinal toxicity in 34.5% and 30% of patients, respectively. No significant differences in incidence and severity of genitourinary and gastrointestinal toxicity were detected between the two IMRT treatment strategies., Conclusion: IMRT/SIB was well-tolerated with favorable rates of acute and late toxicity, both genitourinary and gastrointestinal. Compared to IMRT/C, IMRT/SIB maintained the same efficacy and reduced the overall treatment time., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To test if fotemustine administrated at low doses during the maintenance phase of gioblastoma therapy could improve the toxicity profile, without reducing progression-free survival at six months (PFS-6)., Patients and Methods: Patients enrolled were affected by recurrent glioblastoma multiforme, proven by magnetic resonance imaging (MRI), at least six months after radiochemotherapy completion. Fotemustine was administered at an induction dose of 100 mg/m(2) followed by a maintenance dose of 75 mg/m(2)., Results: All 15 patients completed the induction phase. Eight patients began maintenance-phase therapy and received a median of three cycles (range=2-6). Grade 3 or more haematological toxicity was not documented. The PFS-6 was 5/15 and the median overall survival was 7.5 months., Conclusion: Haematological toxicity compares favourably with trials using the conventional scheme: no grade 3-4 adverse effects were recorded. This low-dose approach could be considered a compromise treatment whilst waiting for definitive standardization of second-line therapy, in order to reduce severe hematological toxicity.

Aim: To investigate whether neoadjuvant-intensified radiochemotherapy improved overall and disease-free survival in patients with locally advanced rectal cancer., Methods: Between January 2007 and December 2011, 80 patients with histologically confirmed rectal adenocarcinoma were enrolled. Tumors were clinically classified as either T3 or T4 and by the N stage based on the presence or absence of positive regional lymph nodes. Patients received intensified combined modality treatment, consisting of neoadjuvant radiation therapy (50.4-54.0 Gy) and infusional chemotherapy (oxaliplatin 50 mg/m(2)) on the first day of each week, plus five daily continuous infusions of fluorouracil (200 mg/m(2) per die) from the first day of radiation therapy until radiotherapy completion. Patients received five or six cycles of oxaliplatin based on performance status, clinical lymph node involvement, and potential risk of a non-sphincter-conserving surgical procedure. Surgery was planned 7 to 9 wk after the end of radiochemotherapy treatment; adjuvant chemotherapy treatment was left to the oncologist's discretion and was recommended in patients with positive lymph nodes. After treatment, all patients were monitored every three months for the first year and every six months for the subsequent years., Results: Of the 80 patients enrolled, 75 patients completed the programmed neoadjuvant radiochemotherapy treatment. All patients received the radiotherapy prescribed total dose; five patients suspended chemotherapy indefinitely because of chemotherapy-related toxicity. At least five cycles of oxaliplatin were administered to 73 patients. Treatment was well tolerated with high compliance and a good level of toxicity. Most of the acute toxic effects observed were classified as grades 1-2. Proctitis grade 2 was the most common symptom (63.75%) and the earliest manifestation of acute toxicity. Acute toxicity grades 3-4 was reported in 30% of patients and grade 3 or 4 diarrhoea reported in just three patients (3.75%). Seventy-seven patients underwent surgery; low anterior resection was performed in 52 patients, Miles' surgery in 11 patients and total mesorectal excision in nine patients. Fifty patients showed tumor downsizing ≥ 50% pathological downstaging in 88.00% of tumors. Out of 75 patients surviving surgery, 67 patients (89.33%) had some form of downstaging after preoperative treatment. A pathological complete response was achieved in 23.75% of patients and a nearly pathologic complete response (stage ypT1ypN0) in six patients. An involvement of the radial margin was never present. During surgery, intra-abdominal metastases were found in only one patient (1.25%). Initially, 45 patients required an abdominoperineal resection due to a tumor distal margin ≤ 5 cm from the anal verge. Of these patients, only seven of them underwent Miles' surgery and sphincter preservation was guaranteed in 84.50% of patients in this subgroup. Fourteen patients received postoperative chemotherapy. In the full analysis of enrolled cohort, eight of the 80 patients died, with seven deaths related to rectal cancer and one to unrelated causes. Local recurrences were observed in seven patients (8.75%) and distant metastases in 17 cases (21.25%). The five-year rate of overall survival rate was 90.91%. Using a median follow-up time of 28.5 mo, the cumulative incidence of local recurrences was 8.75%, and the overall survival and disease-free survival rates were 90.00% and 70.00%, respectively., Conclusion: The results of this study suggest oxaliplatin chemotherapy has a beneficial effect on overall survival, likely due to an increase in local tumor control.