Sodium-glucose cotransporter-2 inhibitors improve cardiovascular outcomes post-acute coronary syndrome complicated by acute heart failure.

Background: Acute coronary syndrome (ACS) remains a risk factor for heart failure (HF). Therefore, we aimed to assess the cardioprotective role of sodium-glucose cotransporter-2 (SGLT2) inhibitors post-ACS in patients with acute HF (AHF) and diabetes. Methods: We conducted a retrospective observational cohort study employing propensity score matching. This study involved patients with diabetes admitted with ACS complicated by AHF, defined as either new clinical HF requiring diuretics during the index admission or having an ejection fraction (EF) of <40%. The study population was divided into two groups; (1) SGLT2 inhibitor users and (2) SGLT2 inhibitor non-users. The Cox proportional hazard regression analysis was used to evaluate the outcomes. Results: A total of 465 patients (93% male; mean age, 55 ± 10 years) were included in this study. Using a 1 : 1 propensity score matching, 78 patients were included per arm with an absolute standardized difference of <0.1 for all baseline characteristics. The use of SGLT2 inhibitors resulted in lower composite outcomes of ACS, HF hospitalization, and all-cause mortality at 1 month and 12 months [1 month: 2.6% vs. 11.5%, HR = 0.20 (0.04-0.94), p = 0.041; 12 months: 14.1% vs. 23.1%, HR = 0.46 (0.22-0.99), p = 0.046]. Conclusion: The findings suggest that SGLT2 inhibitors may confer cardioprotective effects in ACS-induced AHF, thereby widening the spectrum for indications of SGLT2 inhibitors.

Protamine dosing and its impact in cardiac surgery transfusion practice-A retrospective bi-institutional analysis.

BACKGROUND: Bleeding after cardiac surgery is common and continues to require 10-20% of the national blood supply. Transfusion of allogeneic blood is associated with increased morbidity and mortality. Excessive protamine in the absence of circulating heparin after weaning off CPB can cause anticoagulation and precipitate bleeding. Hence, adequate dose calculation of protamine is crucial yet under evaluated. STUDY DESIGN: Retrospective cohort study. METHODS: We conducted a retrospective bi-institutional analysis of cardiac surgical patients who underwent cardiopulmonary bypass (CPB)-assisted cardiac surgery to assess the impact of protamine dosing in transfusion practice. Total 762 patients were identified from two institutions using electronic medical records and the Society of Thoracic Surgery (STS) database who underwent cardiac surgery using CPB. Patients were similar in demographics and other baseline characteristics. We divided patients into two groups based on mg of protamine administered to neutralize each 100 U of unfractionated heparin (UFH)-low-ratio group (Protamine: UFH ≤ 0.8) and high-ratio group (Protamine: UFH > 0.8). RESULTS: We observed a higher rate of blood transfusion required in high-ratio group (ratio >0.8) compared with low-ratio group (ratio ≤0.8) (p < .001). The increased requirement was consistently demonstrated for intraoperative transfusions of red blood cells, plasma, platelets, and cryoprecipitate. CONCLUSION: High protamine to heparin ratio may cause increased bleeding and transfusion in cardiac surgical patients. Protamine to heparin ratio of 0.8 or lower is sufficient to neutralize circulating heparin after weaning off cardiopulmonary bypass.

One Fraction Size Does Not Fit All: Patient Preferences for Hypofractionated Radiation Therapy From a Discrete Choice Experiment.

PURPOSE: Hypofractionated external beam radiation therapy (EBRT) is a standard of care option for localized prostate cancer. To inform clinical practice we quantified patients' preferences for convenience, efficacy, and toxicity risks, of conventional, moderate hypofractionation, and stereotactic radiation therapy regimens. METHODS AND MATERIALS: We used a discrete choice experiment with a voluntary sample consisting of patients treated with EBRT for localized prostate cancer at our academic cancer center. In 2019, 58 participants, mean (SD) age of 72.9 (7.1) years, agreed to complete an in-person 1:1 discrete choice experiment. Each participant made 12 choices between 2 unique EBRT scenarios, each described by 5 attributes: (1) treatment time; (2) fiducial markers; and risk of (3) prostate specific antigen recurrence; (4) acute and (5) late GI or GU toxicity. Patient preferences were estimated using mixed multinomial logistic regression, and prespecified subgroups with conditional logistic regression. RESULTS: All attributes were statistically significant, thus influenced participants' choices. Risks of prostate specific antigen recurrence (ß = -2.581), late (ß = -1.854), and acute (ß = -1.005) toxicity were most important to participants (P < .001 for each), followed by EBRT length (ß = -0.728; P = .017) and fiducial marker implantation (ß = -0.563; P = .004). Older (ß = -0.063; 95% confidence interval, -0.12, -0.01) and rural (ß = -0.083; 95% CI -0.14, -0.02) participants significantly preferred shorter EBRT and were less willing-to-extend treatment to reduce toxicity risk. CONCLUSIONS: Patients with prostate cancer place importance on EBRT attributes, and some are willing to trade-off increased risk of toxicity for improved convenience. Our findings promote shared clinical decision-making because patients are interested in learning about the trade-offs involved.

Increases in Heart Rate Variability Signal Improved Outcomes in Rapid Response Team Consultations: A Cohort Study.

BACKGROUND: Reduced heart rate variability (HRV) indicates dominance of the sympathetic system and a state of "physiologic stress." We postulated that, in patients with critical illness, increases in HRV might signal successful resuscitation and improved prognosis. METHODS: We carried out a prospective observational study of HRV on all patients referred to the rapid response team (RRT) and correlated with serial vital signs, lactate clearance, ICU admission, and mortality. RESULTS: Ninety-one patients were studied. Significantly higher HRV was observed in patients who achieved physiological stability and did not need ICU admission: ASDNN 19 versus 34.5, p=0.032; rMSSD 13.5 versus 25, p=0.046; mean VLF 9.4 versus 17, p=0.021; mean LF 5.8 versus 12.4, p=0.018; and mean HF 4.7 versus 10.5, p=0.017. ROC curves confirmed the change in very low frequencies at 2 hours as a strong predictor for ICU admission with an AUC of 0.772 (95% CI 0.633, 0.911, p=0.001) and a cutoff value of -0.65 associated with a sensitivity of 78.6% and a specificity of 61%. CONCLUSIONS: Reduced HRV, specifically VLF, appears closely related to greater severity of critical illness, identifies unsuccessful resuscitation, and can be used to identify consultations that need early ICU admission.

Adnexal masses in pregnancy: An updated review.

Adnexal masses in pregnancy are not commonly encountered. The majority of these masses are discovered incidentally during routine follow-up. However, some of these masses become symptomatic due to their size, location, and impingement of adjacent structures. Several diagnostic modalities can be utilized for the detection of adnexal masses with different sensitivity and specificity rates. The differential diagnosis of adnexal masses discovered during pregnancy is broad and includes both benign and malignant lesions. The management of such lesions has been a subject of debate for years with no consensus regarding the best management plan. Tumor size, site, and the trimester of mass detection are all crucial in management. In this account, we review adnexal masses discovered in pregnancy, the diagnostic modalities utilized for detecting these lesions, their differential diagnosis, and management strategies.

Repair of Thoracoabdominal Aortic Aneurysm with Thrombosed Infrarenal Component: A Modified Hybrid Technique without Aortic Cross Clamping.

The authors report the successful repair of a Crawford type III thoracoabdominal aortic aneurysm (TAAA) with a thrombosed infrarenal component using a modified hybrid technique without aortic clamping in a high-risk patient. A 64-year-old male with a history of hypertension, diabetes, and severe chronic obstructive pulmonary disease presented with acute on chronic backache and bilateral short distance claudication. A computerized tomography scan demonstrated a large, nonleaking Crawford type III TAAA with thrombosed infrarenal component of the aneurysm. In addition, both common iliac arteries were occluded with the chronic thrombus. A single-stage, modified hybrid procedure involving an aortobifemoral bypass without aortic clamping, debranching of right renal, superior mesenteric, and celiac arteries as well as an endovascular repair of the thoracic aneurysm was performed. Unfortunately, despite a technically sound repair, the patient died postoperatively from a massive pulmonary embolism. TAAA with a thrombosed infrarenal aorta and bilateral common iliac arteries can be repaired using a single-stage modified hybrid procedure without aortic clamping in high-risk patients who cannot tolerate thoracotomy and aortic cross clamping.

Atypical presentation to rocuronium allergy in a 19-year-old female patient.

The danger of anaphylaxis, a rare but life threatening complication of general anesthesia (GA) can be summarized in two: 1. General Anesthesia masks the typical early signs of allergy which can be seen in an awake patient. 2. Anaphylaxis during GA manifests mostly as circulatory/ventilatory failures which can be interpreted as adverse effects of anesthetics or surgery and this can lead to critical delay of effective therapy. A 19-year-old female admitted for posterior spinal fusion and instrumentation (the 5th surgery in patient's life) desaturated seconds after intubation. Cardiopulmonary resuscitation (CPR) was started and the absence of cutaneous signs along with a loud holosystolic murmur were questioned. The patient was promptly resuscitated and allergy to rocuronium was confirmed by intradermal tests 6weeks later. Factors influencing decision making and potential etiology of the newly heard holosystolic murmur during anaphylaxis are discussed.

The incidence of increased ICP in ICU patients with non-traumatic coma as diagnosed by ONSD and CT: a prospective cohort study.

BACKGROUND: Unexplained coma after critical illness can be multifactorial. We evaluated the diagnostic ability of bedside Optic Nerve Sheath Diameter [ONSD] as a screening test for non-traumatic radiographic cerebral edema. METHODS: In a prospective study, mixed medical-surgical intensive care units [ICU] patients with non-traumatic coma [GCS < 9] underwent bedside ultrasonographic ONSD measurements. Non-traumatic radiographic cerebral edema [NTRCE] was defined as > 5 mm midline shift, cisternal, sulcal effacement, or hydrocephalus on CT. RESULTS: NTRCE was identified in 31 of 102 patients [30.4 %]. The area under the ROC curve for detecting radiographic edema by ONSD was 0.785 [95 % CI 0.695-0.874, p <0.001]. ONSD diameter of 0.57 cm was found to be the best cutoff threshold with a sensitivity 84 % and specificity 71 %, AUC 0.785 [95 % CI 0.695-0.874, p <0.001]. Using ONSD as a bedside test increased the post-test odds ratio [OR] for NTRCE by 2.89 times [positive likelihood ratio], whereas post-test OR for NTRCE decreased markedly given a negative ONSD test [ONSD measurement less than 0.57 cm]; negative likelihood ratio 0.22. CONCLUSIONS: The use of ONSD as a bedside test in patients with non-traumatic coma has diagnostic value in identifying patients with non-traumatic radiographic cerebral edema.

Stroke After Radiation Therapy for Head and Neck Cancer: What Is the Risk?

PURPOSE: A retrospective population-based cohort study was conducted to determine the risk of ischemic stroke with respect to time, associated with curative radiation therapy in head and neck squamous cell carcinomas (HNSCC). METHODS AND MATERIALS: On the basis of data from the Ontario Cancer Registry and regional cancer treatment centers, 14,069 patients were identified with diagnoses of squamous cell carcinoma of the oral cavity, larynx, and pharynx who were treated for cure between 1990 and 2010. Hazards of stroke and time to stroke were examined, accounting for the competing risk of death. Stroke risk factors identified through diagnostic and procedural administrative codes were adjusted for in the comparison between treatment regimens, which included surgery alone versus radiation therapy alone and surgery alone versus any exposure to radiation therapy. RESULTS: Overall, 6% of patients experienced an ischemic stroke after treatment, with 5% experiencing a stroke after surgery, 8% after radiation therapy alone, and 6% after any exposure to radiation therapy. The cause-specific hazard ratios of ischemic stroke after radiation therapy alone and after any exposure to radiation therapy compared with surgery were 1.70 (95% confidence interval [CI]: 1.41-2.05) and 1.46 (95% CI: 1.23-1.73), respectively, after adjustment for stroke risk factors, patient factors, and disease-related factors. CONCLUSIONS: Radiation therapy was associated with an increased risk of ischemic stroke compared with surgery alone: for both radiation therapy alone and after all treatment modalities that included any radiation treatment were combined. Because of a shift toward a younger HNSCC patient population, our results speak to the need for adequate follow-up and survivorship care among patients who have been treated with radiation therapy. Advances in treatment that minimize chronic morbidity also require further evaluation.

Free Esophageal Perforation Following Hybrid Visceral Debranching and Distal Endograft Extension to Repair a Ruptured Thoracoabdominal Aortic Aneurysm.

Free esophageal perforation following a hybrid visceral debranching and distal endograft extension to repair a ruptured thoracoabdominal aortic aneurysm (TAAA) is a rare complication. The authors report a 56-year-old male who underwent elective thoracic endovascular aortic repair of a thoracic aneurysm. Four and a half years later, he presented with a new aneurysm extending from the distal end of the thoracic stent graft to the aortic bifurcation involving all the visceral arterial branches. The TAAA ruptured while he was awaiting an elective repair, and as a result, he underwent an emergency hybrid procedure. This involved debranching the visceral arterial branches including autotransplantation of the left kidney and distal endograft extension. Postoperatively, he developed free esophageal perforation secondary to ischemic necrosis requiring esophageal resection and gastric pull-up. The patient was well 6 months after the gastrointestinal restorative procedure. Thus, esophageal perforation following an emergency hybrid repair of ruptured TAAA is a rare complication, and a successful outcome depends on early recognition and surgical exclusion of the ruptured viscus.

Simple Renal Cysts as Markers of Thoracic Aortic Disease.

BACKGROUND: Thoracic aortic aneurysm is usually a clinically silent disease; timely detection is largely dependent upon identification of clinical markers of thoracic aortic disease (TAD); (bicuspid aortic valve, intracranial aortic aneurysm, bovine aortic arch, or positive family history). Recently, an association of simple renal cysts (SRC) with abdominal aortic aneurysm and aortic dissection was established. The aim of our study was to evaluate the prevalence of SRC in patients with TAD in order to assess whether the presence of SRC can be used as a predictor of TAD. METHODS AND RESULTS: We evaluated the prevalence of SRC in 842 patients with TAD (64.0% males) treated at our institution from 2004 to 2013 and compared to a control group of patients (n=543; 56.2% males). Patients were divided into 4 groups: ascending aortic aneurysm (456; 54.2%); descending aortic aneurysm (86; 10.2%); type A aortic dissection (118; 14.0%); and type B aortic dissection (182; 21.6%). SRC were identified by abdominal computed tomography or magnetic resonance imaging of these patients. Prevalence of SRC is 37.5%, 57.0%, 44.1%, and 47.3% for patients with ascending aneurysm, descending aneurysm, type A dissection, and type B dissection, respectively. Prevalence of SRC in the control group was 15.3%. Prevalence of SRC was not significantly different between male and female aortic disease patients, despite reported general male predominance (2:1), which was also observed in our control group (1.7:1). CONCLUSIONS: This study establishes an increased prevalence of SRC in patients with TAD. SRC can potentially be used as a marker for timely detection of patients at risk of TAD.

Current Experience With Acute Type B Aortic Dissection: Validity of the Complication-Specific Approach in the Present Era.

BACKGROUND: Our group proposed in 1992 a "complication-specific approach" for the management of acute aortic dissection type B (TBAD), with uncomplicated cases being treated with medical therapy. In this study, we evaluate the efficacy of this management in in-hospital and postdischarge survival. METHODS: Between 1999 and 2014, 123 consecutive acute TBAD patients were treated at our institution. We compared complicated (rupture/impending rupture, malperfusion, expansion) vs uncomplicated TBAD, as well as TBAD with a dissection flap vs intramural hematoma/penetrating aortic ulcer. RESULTS: A total of 103 patients (84%) were strictly managed according to the complication-specific approach, with 93% in-hospital survival. Twenty deviated from complication-specific approach management (triaged to operation by complication-specific approach, but inoperable for a variety of reasons). Independent risk factors for a complicated course in the dissection flap subgroup (n = 89) were history of coronary artery disease (odds ratio. 3.139; p = 0.04) and maximum aortic diameter exceeding 5 cm (odds ratio, 4.586; p = 0.005). Uncomplicated patients were treated medically with antiimpulse therapy. Among the 103 patients treated with the complication-specific approach, long-term survival was 83%, 78%, 71% and 47% at 1, 3, 5, and 10 years, respectively. Between the uncomplicated and complicated groups, 8-year survival was 55% and 49%, respectively (log-rank p = 0.03). Uncomplicated patients showed comparable 6-year survival (log-rank p = 0.06) to matched normal population controls. CONCLUSIONS: Patients managed with the complication-specific approach showed an overall satisfactory long-term survival over 10 years. No in-hospital deaths occurred in patients with uncomplicated, medically treated acute TBAD, with comparable long-term survival to a matched normal population. These good long-term results provide counterbalancing perspective when considering routine thoracic endovascular aortic repair for all TBAD patients.

Piloting prostate cancer patient-reported outcomesin clinical practice.

PURPOSE: The expanded prostate cancer index composite-26 (EPIC-26) instrument is a validated research tool used for capturing patient-reported quality-of-life outcomes related to the domains of bowel, bladder, and sexual functioning for men undergoing curative treatment for prostate cancer. The purpose of this pilot study was to explore the perceptions and experiences of clinicians with using EPIC-26 in a clinical setting for patients receiving curative radiotherapy. METHODS: Ten clinicians reviewed EPIC-26 scores either before or during weekly clinical encounters with patients receiving curative radiation treatment for prostate cancer. After a period of 2 months, clinicians underwent individual semi-structured interviews where they were asked about their views on measuring patient-reported outcomes in practice, the value of EPIC-26, impressions on patient acceptability, and operational issues. RESULTS: There was a general willingness and acceptance by clinicians to use EPIC-26 for routine clinical practice. Clinician participants found EPIC-26 to be generally informative, and added value to the clinical encounter by providing additional information that was specific to prostate cancer patients. EPIC-26 was also felt to improve overall communication and provide additional insight into the patient experience. CONCLUSIONS: Our qualitative findings suggest that there may be a role for incorporating patient-reported outcome measure assessment tools like EPIC-26 routinely into clinical practice. However, further qualitative and quantitative research is required in order to assess the impact of patient-reported outcome information on communication, patient and clinician satisfaction, and how these and other related outcomes can be used for guiding treatment decision-making.

Genotyping of CYP2C19 polymorphisms and its clinical validation in the ethnic Arab population.

OBJECTIVES: The drug-metabolizing enzymes and transporters (DMET) Plus microarray and x-Tag assays have recently been developed for genotyping individuals in personalized medicine. Furthermore, the cytochrome 450-2C19 (CYP2C19) is a key metabolic enzyme encoded by a polymorphic gene commonly associated with diminished metabolism and variable clinical responses to several drugs in an ethnicity-dependent fashion. Therefore, validation of these clinical procedures as well as knowledge of the ethnic-specific incidences of these gene variants is prerequisite for determining their clinical relevance in any given population. METHODS: We determined the distribution of familiar CYP2C19 variants by the DMET Plus chip in 600 candidates and replicated the findings by the Affymetrix Axiom Genome-Wide Asian Structure Identification Array in 5413 individuals, all Saudis of ethic Arab origin. We then tested the robustness of employing the Luminex xMAP system clinically by comparing the results of genotyping 500 Saudi individuals visiting the Blood Bank of our institution with the findings of the two platforms. KEY FINDINGS: The DMET Plus genotyping revealed that eight of the CYP2C19 variants showed some changes. Thereby, the CYP2C19*17 exhibited the highest minor allele frequency (MAF) of 0.256, followed by the CYP2C19_801 (frequency = 0.055). Six other variants, including the CYP2C19*3, showed MAF in the range of 0.001-0.002. We replicated the frequencies of the CYP2C19*17 and CYP2C19*3, and additionally established that of the CYP2C19*2 (0.099) using the Axiom platform. The xTag genotyping also indicated that 0.834 of the 500 Saudi individuals were extensive metabolizers (*1/*1), 0.158 carried the *1/*2 genotype, 0.01% carried *2/*2 (poor metabolizers) and one each (0.2%) harboured the *1/*8, *2/*3 (intermediate metabolizers) and *8/*8 (poor metabolizers) genotypes. CONCLUSIONS: The results showed reproducible genotyping of the CYP2C19 variants in the Saudi Arab population using two Affymetrix platforms and phenotyping using the Luminex xTag assay. The prevalence of two clinically relevant genotypes (CYP2C19*2 and CYP2C19*3) were similar to other ethnic groups, while that of the CYP2C19*17 was comparably higher.

Vulvar extrauterine endometrial stromal sarcoma: A case report and literature review.

Endometrial stromal sarcoma (ESS) is an extremely rare neoplasm accounting for only 0.2% of all uterine malignancies and for 15-26% of primary uterine sarcomas. The annual incidence of ESS is 1-2 per million women. Herein, to the best of our knowledge, we present the first reported case of ESS of the vulva in a 50-year-old female presenting with per vaginal spotting over a period of three months. Her past surgical history included a subtotal hysterectomy and left salpingo-oophorectomy for uterine fibroids ten years previously. On examination, a 3.5×3×2 cm cystic mass was found in the right labia majora. The mass was excised and the diagnosis of endometrial stromal sarcoma was made. Subsequent metastatic workup was negative and the patient was started on megestrol acetate. She has remained disease free with no signs or symptoms of recurrent or advanced disease for 28 months.

Isolated anterior urethral recurrence of prostatic adenocarcinoma.

Isolated anterior urethral metastases from prostate cancer are rare. The pathogenesis of this form of loco-regional recurrence may be related to spread by instrumentation-induced implantation and could potentially then be associated with a better prognosis than metastatic disease secondary to a more malignant phenotype. We report a case of a 68-year-old man with high-risk prostate cancer, diagnosed at transurethral resection of prostate, who was originally treated with combination external beam radiotherapy and hormonal therapy. He re-presented 4 years after his original diagnosis with recurrent gross hematuria and cystourethroscopic biopsies of anterior urethral polyps revealing isolated recurrent prostatic adenocarcinoma. We present our this case and review the literature.

Using the computed tomography in comparison to the orthogonal radiography based treatment planning in high dose rate (HDR) brachytherapy in cervical uteri cancer patients; a single institution feasibility study.

INTRODUCTION: Brachytherapy is an integral part in the treatment of cervical uteri cancer patients. Orthogonal treatment planning is the standard mode of calculation based on reference points. Introduction of the innovative 3-D computer based treatment planning allows accurate calculation based on volumetric information as regards the target volume and organs at risk (OAR). Also provide dose volume histogram (DVH) for proper estimation of the dose in relation to the volume. AIM: To correlate and compare the information obtained from the two approaches for high dose rate brachytherapy of cervical uteri cancer; the orthogonal conventional method and the computerized tomography (CT) three dimensions (3D) based calculation method in relation to the target and organ at risk (OAR). METHODS: From 6 patients of cervical uteri cancer, 21 applications with orthogonal planning using the Brachy Vision treatment planning system version 7.3.10 were performed. In 10 applications; comparison between orthogonal and CT based planning was done. In orthogonal planning; the dose to point A, rectum and bladder were defined according to the American Brachytherapy Society (ABS) recommendation. From the CT based planning the target volume and dose volume histogram lpar;DVH) were calculated for the clinical target volume (CTV), rectum and bladder. From these two sets, information was obtained and compared and mean values were derived. RESULTS: For dose prescription at point A, an average of 63.5% of CTV received the prescribed dose. The mean ICRU dose to the bladder point is 2.9 Gy+/-1.2 SD (Standard Deviation) and 17% of the bladder volume derived from CT was encompassed by 2.9 Gy isodose line. The mean ICRU dose at the rectum point is 3.4 Gy+/-1.2 SD and 21% of the rectum volume from CT was encompassed by 3.4 Gy isodose line. The maximum dose to the rectum and the bladder derived from the CT and compared to the maximal dose at ICRU is 1.7 and 2.8 times higher than the orthogonal reference points; with the corresponding p value of (p=0.53 and p=0.005) for the rectum and the bladder respectively. CONCLUSIONS: CT based treatment planning for HDR brachytherapy of cervical uteri cancer is reliable and more accurate in definition and calculation of the dose to the target as well as the critical organs. It allows dose calculation based on the actual volume rather than points or bony landmarks.

A randomized study of accelerated fractionation radiotherapy with and without mitomycin C in the treatment of locally advanced head and neck cancer.

OBJECTIVES: This single-institution study evaluates the feasibility of accelerated fractionation radiotherapy (AF) with and without mitomycin C (MMC) in the treatment of locally advanced head and neck cancer. PATIENTS AND METHODS: Between May 1998 and October 2001, sixty patients with locally advanced stage III and IV of head and neck cancer were randomized into three treatment arms: (1) conventional fractionation radiotherapy (CF) (5 fractions per week); (2) accelerated fractionation radiotherapy (AF) (6 fractions per week); and (3) AF plus Mitomycin C (MMC). RESULTS: The 2-year overall survival (OS) of the whole group was 21%. The OS according to treatment arm was 23%, 20%, and 28% in CF, AF, and AF+MMC arms respectively (p<0.19). The 2-year loco-regional control (LC) rate was 22% for the whole group of patients. The LC was 10%, 25%, and 30% for the CF, AF, and AF+MMC respectively (p=0.27). The only significant parameters for OS and LC were performance status and pre-treatment hemoglobin level. Mucositis grades 3 & 4 occurred in 70% and 90% of the patients in the AF and AF+MMC arm respectively compared to 55% of patients in the CF arm (p=0.04). However the addition of MMC did not significantly increase the incidence or severity of mucositis between AF and AF+MMC (p=0.13). Hematological toxicity grades 3 & 4 were significantly higher after MMC (occurred in 40% of patients versus 10% and 5% in CF and AF arms respectively, p=0.04). There was no statistically significant difference in the incidence of grade 3 dryness of mouth (p=0.06), fibrosis (p=0.6), or lymphoedema (p=0.39) among the three arms. CONCLUSION: There was a trend for improvement of LC and OS rates with the use of AF and the addition of MMC to AF compared to CF radiotherapy, although the difference was not statistically significant. The small number of the patients in each treatment arm and the inclusion of multiple tumor sites may contribute to these statistically insignificant results. Accordingly we advise 85 to continue the trial with inclusion of a larger number of patients and restrict tumor sites to one major site.