Difference in toxicity between HIV-positive and HIV-negative patients with squamous-cell cancer of the anal canal treated with concomitant radio-chemotherapy.

BACKGROUND: The incidence of squamous cell carcinoma of the anal canal has been increasing over the last 30 years. HIV has been found to be a risk factor for the development of this disease; radio-chemotherapy (RTCT) may also be more toxic than in HIV-negative patients. The study aims at assessing whether there are any differences in terms of toxicity between HIV-positive and HIV-negative patients treated with concomitant RTCT. METHODS: Search in MEDLINE, EMBASE, CENTRAL (via Cochrane Library-Wiley), DARE, LILACS bibliographic databases. Experimental and analytical observational studies with at least two comparative arms were included: squamous-cell (SC) anal-canal cancer (ACC) treated with RTCT in HIV-positive vs. HIV-negative patients. RESULTS: Fifteen publications, 14 retrospective studies and 1 systematic review, were found. All radiotherapy (RT) techniques and all chemotherapeutic agents used to manage this disease were included. No differences were found in terms of duration (P=0.67) and dose (P=0.53) of RT, while CT results were contradictory. Acute and hematological toxicities were significantly higher in HIV-positive patients, while gastrointestinal, dermatological and chronic toxicities did not significantly differ between the two groups. Given the high heterogeneity of the studies, no objective comparison could be made between studies that included antiretrovirals and those that did not. CONCLUSIONS: HIV-positive patients may be at higher risk for acute and hematological toxicity than HIV-negative patients. A precise conclusion cannot be drawn on the use of antiretrovirals, given the high heterogeneity of data.

Oncogenic role of arsenic exposure in lung cancer: A forgotten risk factor.

Several drinkable water sources worldwide have been highly contaminated with arsenic, which means that an estimated 160 million people have been exposed to this chemical agent. If we analyse exposure by region, we will find a high correlation between arsenic contamination and the incidence of lung cancer (among other malignancies). In order to determine what the risks of these exposures are, we need to understand how this chemical is processed in our body and how it is linked to cancer. In this article we reviewed how biotransformation of ingested arsenic may lead to cancer by modulating the activation of several essential signalling pathways such as EGFR, PI3K/AKT, RTK/Ras/PI3K, JNK/STAT3 and Nrf2-KEAP1; by producing epigenetics modifications and by disrupting normal expression of miRNAs. In order to design effective health policies, educational strategies, decontaminations plans and effective medical treatments are necessary to understand the impact of arsenic pollution and the relevance of the environment in our health.

Stereotactic Radiosurgery for the Treatment of Recurrent High-grade Gliomas: Long-term Follow-up.

High-grade gliomas (HGG) are the most frequent primary central nervous system tumors; treatment of HCGs includes surgery and post-operative conformal radiotherapy associated with temozolomide (TMZ or procarbazine/lomustine/vincristine [PCV], specifically in patients with anaplastic oligodendrogliomas or anaplastic oligoastrocytomas). However, recurrence is common. Re-irradiation has been utilized in this setting for years and remains a feasible option, although there is always a concern regarding toxicity. Modern high-precision conformal techniques, including stereotactic radiosurgery (SRS), could improve the therapeutic ratio by delivering high biologically equivalent doses while reducing high-dose radiotherapy (RT) to normal brain tissue. In this paper, we present the results obtained after prolonged follow-up in patients who underwent SRS as a treatment for recurrent high-grade gliomas at San Francisco Hospital in Madrid, Spain.

What is the evidence for the clinical value of SBRT in cancer of the cervix?

AIM: The aim of this review is to describe and analyze indications and results of the use of SBRT in uterine cervix cancer, reviewing articles published from January 2010 up to August 2017, for any one of the four indications listed:1Patient refusal or anatomic impediments to interstitial or intracavitary brachytherapy (BCT), i.e. SBRT as an "alternative" for BCT;2Patients with voluminous tumors, or asymmetric tumors where BCT alone would not achieve curative doses, i.e. SBRT as a primary adjunct to BCT;3Pelvic and para aortic adenopathy where SBRT could be used as a boost, i.e. SBRT as a primary adjunct to external beam pelvic radiotherapy;4Small volume recurrences (postoperative or post radiotherapy), i.e. SBRT for salvage. BACKGROUND: Cervix cancer standard treatment involves pelvic irradiation and chemotherapy, recent advances in irradiation techniques might offer new possible approaches. MATERIAL AND METHODS: Systematic review of the English language literature about Cervix cancer, SBRT, published from January 2010 to January 2018 identified through a database search of PubMed, and Ovid MEDLINE, using pre-defined search phrases. RESULTS: The results in the literature, in general, demonstrate rather weak efficacy of SBRT. In this review, we did not find strong evidence to recommend routine SBRT as a primary treatment for cervico-uterine cancers, i.e. as a replacement for BCT; in highly selected cases it might be considered useful as salvage therapy for relapsed cervix cancer. CONCLUSION: The existing data to not warrant recommending SBRT for the definitive treatment of cervix cancer, but may have some value in the recurrent/relapsed setting.

The synergistic effect of radiotherapy and immunotherapy: A promising but not simple partnership.

Radiotherapy (RT) is one of the main components in the treatment of cancer. The better understanding of the immune mechanisms associated with tumor establishment and how RT affects inflammation and immunity has led to the development of novel treatment strategies. Several preclinical studies support the use of RT in combination with immunotherapy obtaining better local and systemic tumor control. Current ongoing studies will provide information about the optimal RT approach, but the development of reliable predictors of the response from the preclinical and the early phases of clinical studies is necessary to avoid discarding treatment strategies with significant clinical benefit. This review summarize the current concepts of the synergism between RT and immunotherapy, the molecular effects of RT in the tumor microenvironment, their impact on immune activation and its potential clinical applications in trials exploring this important therapeutic opportunity. Finally, the potential predictors of clinical response are discussed.

Recomendaciones sobre el manejo del cáncer de páncreas tipo adenocarcinoma en Latinoamérica: Reunión del Consenso del Simposio Latinoamericano de Gastroenterología Oncológica (SLAGO) y de la Asociación Ibero Latinoamericana de Terapia Radiante (ALATRO), Viña del Mar, Chile 2015 / Recommendations for the management of pancreatic cancer type adenocarcinoma: A consensus statement reached during the 2015 Latin American Symposium on Gastroenterological Oncology

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.

[Recommendations for the management of pancreatic cancer type adenocarcinoma: A consensus statement reached during the 2015 Latin American Symposium on Gastroenterological Oncology]. / Recomendaciones sobre el manejo del cáncer de páncreas tipo adenocarcinoma en Latinoamérica: Reunión del Consenso del Simposio Latinoamericano de Gastroenterología Oncológica (SLAGO) y de la Asociación Ibero Latinoamericana de Terapia Radiante (ALATRO), Viña del Mar, Chile 2015.

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.

Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer.

BACKGROUND: The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown. METHODS: We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer. RESULTS: Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P=0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P=0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). Acute side effects of regional nodal irradiation were modest. CONCLUSIONS: In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.).

Intraoperative radiotherapy for gastrointestinal malignancies: contemporary outcomes with multimodality therapy.

The integration of intraoperative radiotherapy (IORT) into the multimodal treatment of gastrointestinal cancer is feasible and leads to high rates of local control. In-field tumoral control using IORT-containing strategies can be achieved in over 90 % of most cases, regardless of the site or status of the tumor (primary or recurrent). Electron beam IORT, or intraoperative electron radiation therapy, is the dominant technology used in institutions reporting data in publications the 21st century. Neither surgery nor systemic therapy is compromised by the integration of IORT-containing radiotherapy.

Dosimetric evaluation of 3-D conformal and intensity-modulated radiotherapy for breast cancer after conservative surgery.

BACKGROUND: Breast cancers are becoming more frequently diagnosed at early stages with improved long term outcomes. Late normal tissue complications induced by radiotherapy must be avoided with new breast radiotherapy techniques being developed. The aim of the study was to compare dosimetric parameters of planning target volume (PTV) and organs at risk between conformal (CRT) and intensity-modulated radiation therapy (IMRT) after breast-conserving surgery. MATERIALS AND METHODS: A total of 20 patients with early stage left breast cancer received adjuvant radiotherapy after conservative surgery, 10 by 3D-CRT and 10 by IMRT, with a dose of 50 Gy in 25 sessions. Plans were compared according to dose-volume histogram analyses in terms of PTV homogeneity and conformity indices as well as organs at risk dose and volume parameters. RESULTS: The HI and CI of PTV showed no difference between 3D-CRT and IMRT, V95 gave 9.8% coverage for 3D-CRT versus 99% for IMRT, V107 volumes were recorded 11% and 1.3%, respectively. Tangential beam IMRT increased volume of ipsilateral lung V5 average of 90%, ipsilateral V20 lung volume was 13%, 19% with IMRT and 3D-CRT respectively. Patients treated with IMRT, heart volume encompassed by 60% isodose (30 Gy) reduced by average 42% (4% versus 7% with 3D-CRT), mean heart dose by average 35% (495 cGy versus 1400 cGy with 3D-CRT). In IMRT minimal heart dose average is 356 cGy versus 90 cGy in 3D-CRT. CONCLUSIONS: IMRT reduces irradiated volumes of heart and ipsilateral lung in high-dose areas but increases irradiated volumes in low-dose areas in breast cancer patients treated on the left side.

Bibliometrics of intraoperative radiotherapy: analysis of technology, practice and publication tendencies.

PURPOSE: To analyze the performance and quality of intraoperative radiation therapy (IORT) publications identified in medical databases during a recent period in terms of bibliographic metrics. MATERIALS AND METHODS: A bibliometric search was conducted for IORT papers published in the PubMed database between 1997 and 2013. Publication rate was used as a quantity indicator; the 2012 Science Citation Index Impact Factor as a quality indicator. Furthermore, the publications were stratified in terms of study type, scientific topic reported, year of publication, tumor type and journal specialty. We performed a one-way analysis of variance (ANOVA) to determine differences between the means of the analyzed groups. RESULTS: Among the total of 207 journals, articles were reported significantly more frequently in surgery (n = 399, 41 %) and radiotherapy journals (n = 273, 28 %; p < 0.01). The highest impact factor was achieved by clinical oncology journals (p < 0.01). The majority of identified articles were retrospective cohort reports (n = 622, 64 %), followed by review articles (n = 204, 21 %; p < 0.001). Regarding primary topic, reports on cancer outcome following specific tumor therapy were most frequently published (n = 661, 68 %; p < 0.001) and gained the highest mean impact factor (p < 0.01). Gastrointestinal tumor reports were represented most frequently (n = 456, 47 %; p < 0.001) and the mean superior impact factor was earned by breast and gynecologic publications (p < 0.01). CONCLUSION: We identified a consistent and sustained scientific productivity of international IORT expert groups. Most publications appeared in journals with surgical and radiooncological content. The highest impact factor was achieved by medical oncology journals.

Stereotactic radiosurgery in patients with multiple intracranial meningiomas.

PURPOSE: Stereotactic radiosurgery (SRS) delivers a potent, highly focused dose of radiation to the tumor while sparing the surrounding normal tissues. The purpose of this study was to assess the outcome of patients with intracranial meningiomas treated with SRS. METHODS: A total of 73 patients with 221 benign meningiomas treated between 1991 and 2005 with SRS and followed up for more than a year were reviewed. Fifty patients (68%) were treated with SRS to the primary meningioma while 23 (32%) received SRS to relapsing tumors adjacent or distant from the site of the initial meningioma that was previously treated with surgery alone. Mean tumor margin dose was 14 Gy (range 10-16). SRS was delivered after surgery in 117 meningiomas (55 patients). RESULTS: The median age at diagnosis was 47 years (range 16-74) and the median follow-up 5.8 years (range 1-13.6). The 3- and 5-year overall survival (OS) rates for all patients were 95% and 90%, respectively. The mean gross tumor volume decreased from 4.17 cm3 to 3.23 cm(3) after SRS (p=0.057). Twenty-two (10%) meningiomas increased after SRS. In addition, clinical symptoms improved in 36% and remained stable in 45% of the patients. With regard to morbidity of SRS, only 7 patients (9.6%) had late complications, including edema (N=4), brain necrosis (N=4), gliosis (N=1), and paresis of the III pair nerve (N=1). There was no treatment-related mortality. CONCLUSION: SRS for patients with multiple intracranial meningiomas is effective yielding a high rate of local tumor control, whereas treatment-related morbidity remains low.

GERICO-03 phase II trial of accelerated and partial breast irradiation in elderly women: feasibility, reproducibility, and impact on functional status.

PURPOSE: To analyze the feasibility, reproducibility, and impact on functional status of postoperative accelerated and partial breast irradiation (APBI) using interstitial high-dose rate-brachytherapy in women older than 70 years. METHODS AND MATERIALS: From July 2004 to April 2008, 46 patients were screened for enrollment in a nationwide prospective Phase II trial. A total of 40 patients were eligible according to the inclusion criteria (aged >70 years, T1-2 <30mm, and pN0). The total delivered dose was 34Gy of 10 fractions for 5 days. Feasibility and reproducibility were evaluated using a Quality Index (QI) defined as (V100%-clinical target volume)/V100%. Skin toxicity was reported using Common Terminology Criteria for Adverse Events version 3.0. ABPI impact on functional dependence was evaluated using the Activity of Daily Living and Instrumental Activity of Daily Living scales. Reproducibility and feasibility were assessed with the optimal two-stage design of Simon. RESULTS: Median age was 74 years (70-87 years). All patients were treated according to the protocol. Median Quality Index calculated for the 40 eligible patients was 13.3% (1-70%). It was considered acceptable, partially acceptable, and nonacceptable in 10, 28, and 2 patients, respectively. Within 12 months after APBI, overall rates of toxicity were 59%, 28%, and 2% for Grade 1, 2, and 3 events, respectively. Twelve months after APBI, 35 patients (87%) achieved excellent/good cosmetic result. Compared with baseline values, Activity of Daily Living and Instrumental Activity of Daily Living scores remained unchanged 6 and 12 months after APBI. CONCLUSIONS: APBI by means of high-dose rate-brachytherapy is a feasible/reproducible technique without significant impact on functional dependence in the treatment of elderly women with early breast cancer.

Intra-operative electron beam radiotherapy for newly diagnosed and recurrent malignant gliomas: feasibility and long-term outcomes.

INTRODUCTION: Intra-operative electron beam radiotherapy (IOERT) is an alternative to dose escalation for the treatment of central nervous system tumors. The objective of this study was to describe the feasibility and long-term outcomes of IOERT in the treatment of primary and recurrent gliomas. MATERIALS AND METHODS: From January 1992 through December 2002, all patients treated with IOERT at the Hospital San Francisco de Asis, Madrid/Spain were retrospectively reviewed. The selection criteria included patients with superficial tumors, KPS >70 % and lesions <6 cm. Irradiation was administered in one section. The prescribed dose considered the amount of post-resection residual tumor, previous radiotherapy and the tolerance level of brain structures exposed to IOERT. RESULTS: There were 17 patients (53 %) with newly diagnosed malignant brain gliomas and 15 patients with recurrent tumors. The delivered dose varied from 8 to 20 Gy (median 12.5 Gy) for primary and from 8 to 16 Gy (median 10 Gy) for recurrent tumors. The median overall survival for the entire cohort was 13 months (14 and 10.4 months for the primary and recurrent, respectively). Three patients presented with radionecrosis, one patient with osteomyelitis at the craniotomy bone flap, one with intracerebral hemorrhage, and another patient experienced a pulmonary embolism. CONCLUSIONS: IOERT is a feasible technique and can be viewed as a tool in the treatment of newly diagnosed or recurrent brain gliomas.

Hypofractionated helical tomotherapy using 2.5-2.6 Gy daily fractions for localized prostate cancer.

BACKGROUND: The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer. MATERIALS AND METHODS: We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. RESULTS: Thirty-two patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median age at diagnosis was 69 years (range 49-87) and the median follow-up 11 months (range 7-40). Grade 2 acute GI toxicity occurred in 9 patients (19 %). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6 % of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6 Gy/fraction or those who received a total radiation dose ≥70 Gy had higher rates of grade ≥2 acute GU toxicity (P = 0.004 and P = 0.048, respectively). CONCLUSION: Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control.

Clinical and technological transition in breast cancer.

This article is a summary of the conference "Clinical and technological transition in breast cancer" that took place in the Congress of the Spanish Society of Radiation Oncology, placed in Vigo (Spain) on June 21, 2013. Hugo Marsiglia and Philip Poortmanns were the speakers, the first discussed about "Clinical and technological transition" and the second about "EORTC clinical trials and protocols".

Higher toxicity with 42 Gy in 10 fractions as a total dose for 3D-conformal accelerated partial breast irradiation: results from a dose escalation phase II trial.

OBJECTIVE: Recent recommendations regarding indications of accelerated partial breast irradiation (APBI) have been put forward for selected breast cancer (BC) patients. However, some treatment planning parameters, such as total dose, are not yet well defined. The Institut Gustave Roussy has initiated a dose escalation trial at the 40 Gy/10 fractions/5 days and at a further step of total dose (TD) of 42 Gy/10 fractions/ 5 days. Here, we report early results of the latest step compared with the 40 Gy dose level. METHODS AND MATERIALS: From October 2007 to March 2010, a total of 48 pT1N0 BC patients were enrolled within this clinical trial: 17 patients at a TD of 42 Gy/10f/5d and 31 at a TD of 40 Gy/10f/5d. Median follow-up was 19 months (min-max, 12-26). All the patients were treated by APBI using a technique with 2 minitangents and an "enface" electrons delivering 20% of the total dose. Toxicities were systematically assessed at 1; 2; 6 months and then every 6 months. RESULTS: Patients' recruitment of 42 Gy step was ended owing to persistent grade 3 toxicity 6 months after APBI completion (n = 1). Early toxicities were statistically higher after a total dose of 42 Gy regarding grade ≥2 dry (p = 0.01) and moist (p = 0.05) skin desquamation. Breast pain was also statistically higher in the 42 Gy step compared to 40 Gy step (p = 0.02). Other late toxicities (grade ≥2 fibrosis and telangectasia) were not statistically different between 42 Gy and 40 Gy. CONCLUSIONS: Early toxicities were more severe and higher rates of late toxicities were observed after 42 Gy/10 fractions/5 days when compared to 40 Gy/10 fractions/5 days. This data suggest that 40 Gy/10 fractions/ 5 days could potentially be the maximum tolerance for PBI although longer follow-up is warranted to better assess late toxicities.

Phase II trial of 3D-conformal accelerated partial breast irradiation: lessons learned from patients and physicians' evaluation.

INTRODUCTION: The present study prospectively reported both physicians' and patients' assessment for toxicities, cosmetic assessment and patients' satisfaction after 3D-conformal accelerated partial breast irradiation (APBI). MATERIALS AND METHODS: From October 2007 to September 2009, 30 early breast cancer patients were enrolled in a 3D-conformal APBI Phase II trial (40 Gy/10 fractions/5 days). Treatment related toxicities and cosmetic results were assessed by both patients and physicians at each visit (at 1, 2, 6 months, and then every 6 months). Patient satisfaction was also scored. RESULTS: After a median follow-up of 27.7 months, all patients were satisfied with APBI treatment, regardless of cosmetic results or late adverse events. Good/excellent cosmetic results were noticed by 80% of patients versus 92% of cases by radiation oncologists. Breast pain was systematically underestimated by physicians (8-20% vs. 16.6-26.2%; Kappa coefficient KC=0.16-0.44). Grade 1 and 2 fibrosis and/or breast retraction occurred in 7-12% of patients and were overestimated by patients (KC=0.14-0.27). CONCLUSIONS: Present results have shown discrepancies between patient and physician assessments. In addition to the assessment of efficacy and toxicity after 3D-conformal APBI, patients' cosmetic results consideration and satisfaction should be also evaluated.

Effect of preoperative rescue concomitant FUN/XUN-based chemo-radiotherapy for neoadjuvant chemotherapy-refractory breast cancer.

Even though tumor progression under neoadjuvant chemotherapy is uncommon, its locoregional management remains absolutely unclear. What is the best time for radical surgery or radiotherapy? "Rescue" chemo-radiotherapy could be a suitable radiosensitizing strategy to further reduce tumor progression and allow curative surgery while maintaining systemic therapy.