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.).

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.

[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.

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.

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.

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".

New perspectives in radiation oncology: Young radiation oncologist point of view and challenges.

AIM: To assess the role of the young radiation oncologist in the context of important recent advancements in the field of radiation oncology, and to explore new perspectives and competencies of the young radiation oncologist. BACKGROUND: Radiation oncology is a field that has rapidly advanced over the last century. It holds a rich tradition of clinical care and evidence-based practice, and more recently has advanced with revolutionary innovations in technology and computer science, as well as pharmacology and molecular biology. MATERIALS AND METHODS: Several young radiation oncologists from different countries evaluated the current status and future directions of radiation oncology. RESULTS: For young radiation oncologists, it is important to reflect on the current practice and future directions of the specialty as it relates to the role of the radiation oncologist in the comprehensive management of cancer patients. Radiation oncologists are responsible for the radiation treatment provided to patients and its subsequent impact on patients' quality of life. Young radiation oncologists must proactively master new clinical, biological and technical information, as well as lead radiation oncology teams consisting of physicists, dosimetrists, nurses and technicians. CONCLUSIONS: The role of the young radiation oncologist in the field of oncology should be proactive in developing new competencies. Above all, it is important to remember that we are dealing with the family members and loved ones of many individuals during the most difficult part of their lives.

Primary squamous cell carcinoma of the breast: A rare case report.

BACKGROUND: Squamous cells are normally not found inside the breast. Therefore, a primary squamous cell carcinoma of the breast is an exceptional phenomenon and the management of this type of disease is still debated. AIM: Clinical outcome assessment of a patient with squamous cell carcinoma of the breast. MATERIALS AND METHODS: We report a case of primary squamous cell carcinoma of the breast (T1cN0M0) in a 51-years-old woman who underwent breast conserving surgery plus adjuvant chemotherapy and radiation therapy (RT). RESULTS: With a follow up of 43 months, the patient is alive with no evidence of local or distant recurrence. The patient had Grade 2 acute skin toxicity. No late skin or respiratory toxicity was observed. CONCLUSIONS: Pure primary squamous cell carcinoma of the breast is a rare and aggressive disease, often treatment-refractory. Our case shows that the addition of RT after breast conserving surgery, allows to achieve a high local control without adding severe toxicity. A multidisciplinary approach seems to be the optimal management for early stages in this rare disease.

Outcome for patients with essential trigeminal neuralgia treated with linear accelerator stereotactic radiosurgery.

BACKGROUND: Stereotactic radiosurgery (SRS) is one option for treatment of trigeminal neuralgia, after unsuccessful conservative approaches. OBJECTIVES: The objective of this study was to retrospectively evaluate our institutional results in the management of patients with idiopathic trigeminal neuralgia treated with linear accelerator SRS. METHODS: Fifty-two patients were treated between January 1998 and December 2009 and were followed for more than 6 months (median: 26.6 months). Forty-seven patients (90%) had undergone previous surgery before SRS. The target dose ranged from 50 to 80 Gy. RESULTS: After SRS, 9 patients presented complete remission of the pain, and 21 were pain free but still under medication. Eleven patients reported a relief of more than 50% in crisis frequency. In 9 patients, no significant improvements were seen, and 2 presented an exacerbation of the pain. After an average period of 20 months, 15 patients reported pain recurrence. Results were better in patients older than 60 years (p = 0.019). Nineteen patients presented facial numbness after SRS, with a trend toward favorable treatment response (p = 0.06). CONCLUSION: SRS is an effective alternative to the treatment of essential trigeminal neuralgia, with long-lasting pain relief in more than 50% of the patients. Better results were seen with patients aged more than 60 years.

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.

Phyllodes tumor of the breast.

PURPOSE: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. METHODS AND MATERIALS: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapy (RT). RESULTS: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size < or = 3 cm and no tumor necrosis for overall survival. In the malignant and borderline subgroup multivariate analysis TM was the only favorable independent prognostic factor for disease-free survival. CONCLUSIONS: This study showed that phyllodes tumor patients with no RD after treatment have better local control. Benign tumors have a good prognosis after surgery alone. In borderline and malignant tumors, TM had better results than BCS. Thus, in these forms adjuvant RT should be considered according to histologic criteria.

Scintigraphic evaluation of oesophageal transit during radiotherapy to the mediastinum.

BACKGROUND: To quantitatively evaluate radiation-induced impaired oesophageal transit with oesophageal transit scintigraphy and to assess the relationships between acute oesophagitis symptoms and dysmotility. METHODS: Between January 1996 and November 1998, 11 patients affected by non-small-cell carcinoma of the lung not directly involving the oesophagus, requiring adjuvant external beam radiotherapy (RT) to the mediastinum were enrolled. Oesophageal transit scans with liquid and semisolid bolus were performed at three pre-defined times: before (T0) and during radiation at 10 Gy (T1) and 30 Gy (T2). Two parameters were obtained for evaluation: 1) mean transit time (MTT); and 2) ratio between peak activity and residual activity at 40 seconds (ER-40s). Acute radiation toxicity was scored according to the joint EORTC-RTOG criteria. Mean values with standard deviation were calculated for all parameters. Analysis of variance (ANOVA) tests and paired t-Tests for all values were performed. RESULTS: An increase in the ER-40s from T0 to T1 or T2 was seen in 9 of 11 patients (82%). The mean ER-40s value for all patients increased from 0.8306 (T0) to 0.8612 (T1) and 0.8658 (T2). These differences were statistically significant (p < 0.05) in two paired t-Tests at T0 versus T2 time: overall mean ER-40s and upright ER-40s (p = 0.041 and p = 0.032, respectively). Seven patients (63%) showed a slight increase in the mean MTT value during irradiation but no statistically significant differences in MTT parameters were found between T0, T1 and T2 (p > 0.05). CONCLUSION: Using oesophageal scintigraphy we were able to detect early alterations of oesophageal transit during the third week of thoracic RT.

Preoperative bi-fractionated accelerated radiation therapy for combined treatment of locally advanced rectal cancer in a consectutive series of unselected patients.

BACKGROUND: although preoperative RT (Radiation Therapy) is becoming the preferred approach for combined treatment of locally advanced rectal adenocarcinoma, no regimen can be now considered as a standard. Since the toxicity of preoperative RT isn't yet completely known, and the advantages of preoperative RT could be counterbalanced by increased postoperative morbidity and mortality, a monocentre series of preoperative bifractionated accelerated RT was retrospectively reviewed to clarify toxicity and outcomes after a prolonged follow up. METHODS: patients were screened following these eligibility criteria: histology-proven adenocarcinoma of the rectum; distal tumour extent at 12 cm or less from the anal verge; clinical stage T3-4/anyN, or anyT/N1-2; ECOG Performance Status 0-2. A total dose of 41.6 Gy (26 twice daily fractions of 1.6 Gy) was delivered. Surgery was carried out 17 +/- 2 days after RT completion, adopting the total mesorectal excision technique. RESULTS: 24 men and 23 women were enrolled; median age was 55 years (r.: 39-77). Twenty-eight patients were stage II and 19 stage III. 9 patients suffered from a recurrent tumour. 2 patients experienced a severe grade 4 gastrointestinal toxicity (a colo-vaginal fistula and an intestinal obstruction, both successfully treated). Operative mortality was nil; postoperative early complications occurred in 13 cases; mean length of hospital stay was 15 days. After a mean follow up of 44 months (r.: 18-84) 8 patients had deceased for recurrent disease, 15 were alive with a disease progression (2 pelvic recurrences and 13 pure distant deposits) and 24 were alive, without disease. The 5-year actuarial overall survival was 74.2%, the disease-free survival 62.9% and the regional control rate 84.7%. Long-term complications included 1 case of radiation enteritis requiring surgery, 2 cases of anastomotic stricture and 3 cases of bladder incontinence. CONCLUSION: bifractionated accelerated RT administered in the preoperative setting to patients bearing locally advanced rectal cancer is reliable and safe, as its immediate and late toxicity (mainly infectious) is acceptably low and long-term survivals are achievable. These findings support the increasing use of preoperative RT for treatment of this malignancy in experienced centres. Ongoing multicentric trials are expected to address still unsolved issues, including the benefit of CT adjunct to preoperative RT.

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.

Medullary breast carcinoma: a case report with cytological features and histological confirmation.

We report the case of a 83-year-old woman who presented with a left-breast lump. On physical examination the patient had a well-demarcated mass located in the upper outer quadrant of her left breast with a palpable unilateral axillary lymph node. Mammography and ultrasonography depicted a heterogeneous well-defined lesion measuring 6 cm in diameter without calcifications. Fine-needle aspiration cytology of the lesion was performed. Cytological examination revealed highly cellular smears containing large atypical cells arranged in syncytial sheets and intimately admixed with lymphocytes and neutrophils. The nuclear to cytoplasmic ratio was high in tumor cells whose nucleus exhibited coarse chromatin with one or more conspicuous nucleoli. The diagnosis of medullary breast carcinoma, which was strongly suspected by cytology, was confirmed by histological examination of the surgical specimen after a modified radical mastectomy with axillary dissection.

Breast cancer with synchronous metastases: trends in survival during a 14-year period.

PURPOSE: Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis. PATIENTS AND METHODS: A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by chi(2) test, log-rank test, and Cox regression analysis. RESULTS: Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P <.001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P <.001). CONCLUSION: The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.