More Is Not Better When It Comes to Treating Rectal Cancer With Multimodal Chemoradiation Beyond the Standard Radiation Dose of 5040 cGy.

BACKGROUND: Radiation dose schedules for neoadjuvant chemoradiation for rectal cancers differ, with the most common dose schedule using 5040 cGy in 28 fractions. OBJECTIVES: The aim of this retrospective study was to assess the benefit of higher radiation doses beyond 5040 cGy in the context of pathological response and follow-up events. SETTING: The database from a provincial tertiary cancer center in Canada was the source of information for this study. PATIENTS: Included in this study were 508 consecutive patients with rectal cancer with locally advanced disease (clinical T3/T4 or N1/N2) who received neoadjuvant chemoradiation followed by surgery. Of the 508 patients, 281 received the standard radiation dose of 4500 to 5040 cGy and 227 received a dose >5040 cGy. MAIN OUTCOME MEASURE: The postsurgical pathology, late toxicities, and follow-up outcomes were analyzed. The outcomes were evaluated in relation to the dose of radiation received. RESULTS: Data regarding the clinical outcomes were comparable between the 4500 to 5040 cGy and >5040 cGy radiation groups with pathological complete response rates of 20.9% and 15.4% (p = 0.104); distant recurrence rates of 17.4% and 19.4% (p = 0.36); local recurrence rates of 3.2% and 3.5% (p = 0.36); and the median overall survival rates of 61 and 60.5 months (p = 0.8). No statistically significant correlation of improvement in outcomes was noted with radiation doses beyond 5040 cGy. LIMITATIONS: This is a retrospective study. CONCLUSION: Our study showed that dose escalation beyond the standard dose of 4500 to 5040cGy failed to achieve meaningful clinical outcomes. See Video Abstract at http://links.lww.com/DCR/B633. MS NO ES MEJOR CUANDO SE TRATA DE TRATAR EL CNCER DE RECTO CON QUIMIORRADIACIN MULTIMODAL MS ALL DE LA DOSIS DE RADIACIN ESTNDAR DE CGY: ANTECEDENTES:En neoadyuvancia de cáncer rectal es posible encontrar muchas variaciones, en radioterapia la dosis más común que usa 5040 cGy en 28 fracciones.OBJETIVOS:El objetivo de este estudio retrospectivo fue evaluar el beneficio de dosis de radiación más altas más allá de 5040cGy en el contexto de la respuesta patológica y en su seguimiento.AJUSTE:Base de datos de un centro de cáncer terciario provincial en Canadá.PACIENTES:Se incluyeron en este estudio quinientos ocho pacientes consecutivos con cáncer de recto y enfermedad localmente avanzada (clínica T3 / T4 o N1 / N2) que recibieron quimiorradiación neoadyuvante seguida de cirugía. De los 508 pacientes, 281 recibieron la dosis de radiación estándar de 4500-5040 cGy y 227 recibieron una dosis > 5040 cGy.PRINCIPAL MEDIDA DE RESULTADO:Se analizo evolucion posquirúrgica, toxicidad tardía y seguimiento. Los resultados se evaluaron en relación con la dosis de radiación recibida.RESULTADOS:Los datos con respecto a los resultados clínicos fueron comparables entre los grupos de radiación de 4500-5040 cGy y> 5040 cGy con tasas de respuesta patológica completa de 20,9% y 15,4% respectivamente (p = 0,104); tasas de recurrencia a distancia de 17,4% y 19,4%, respectivamente (p = 0,36); tasas de recurrencia local de 3,2% y 3,5%, respectivamente (p = 0,36); y la mediana de las tasas de supervivencia global de 61 y 60,5 meses, respectivamente (p = 0,8). No se observó una correlación estadísticamente significativa de mejoría en los resultados con dosis de radiación superiores a 5040 cGy.LIMITACIONES:Este es un estudio retrospectivo.CONCLUSIONES:Nuestro estudio mostró que el aumento de la dosis más allá de la dosis estándar de 4500-5040cGy no logró resultados clínicos significativos. Consulte Video Resumen en http://links.lww.com/DCR/B633. (Traducción-Dr. Gunther Bocic).

PD-1 Blockade With Concurrent Radiotherapy for Locally Advanced Inoperable Cutaneous Squamous Cell Carcinoma.

INTRODUCTION: For patients with locally advanced cutaneous squamous cell carcinoma (LA-cSCC), radiotherapy alone (RT) is often the only treatment option with modest tumor response. We report the outcomes of using combination of programmed cell death protein-1 (PD-1) inhibitor and RT in the treatment of inoperable LA-cSCC. The study presents the efficacy and safety data for the patients with LA-cSCC treated with this combination. METHODS: During the period 2018-2020, a total of 7 patients with biopsy proven inoperable LA-cSCC were treated with combination of PD-1 inhibitor cemiplimab and concurrent RT (Cem-RT). The patients were followed up for safety and efficacy of the Cem-RT regimen and the primary endpoints were objective tumor response and toxicity. RESULTS: The median age of patients was 68 years (range, 64-94). All patients had ECOG performance score 0-1. Six patients initially received cemiplimab and concurrent RT was added to PD-1 inhibitor when there was an inadequate therapeutic response. One patient received concurrent Cem-RT. RT with PD-1 antibody was well tolerated. Six patients developed grade ≤2 dermatitis and 1 patient (patient no. 3) developed acute grade 3 skin reaction. During the post-RT follow up, 3 patients discontinued cemiplimab due to significant toxicities. At the time of reporting , 5 patients remain in complete remission. One patient developed lung metastasis and is currently receiving best supportive care. CONCLUSIONS: The Cem-RT combination was safe and well tolerated with significant tumor response suggesting Cem-RT may be a viable therapeutic option for LA-cSCC. Our hypothesis generating data support the rationale for future prospective studies.

Impact of dose-capping chemotherapy in concurrent chemoradiotherapy in rectal cancer patients.

INTRODUCTION: The study evaluated the effect of chemotherapy dose-capping on disease recurrence, toxicity and survival of rectal cancer patients treated with chemoradiotherapy (CRT). METHODS: 601 consecutive rectal cancer patients treated with concurrent CRT were retrospectively analysed. Dose-capped patients were defined as having a body surface area (BSA) ≥2.0 m2 and who received <95% full weight-based chemotherapy dose. Binary logistic regression was used to study the factors associated with the outcome variables (capped vs. uncapped). Kaplan-Meier estimation evaluated significant predictors of survival. RESULTS: The median follow-up time was 7.54 years. The rate of disease recurrence was significantly higher in dose-capped patients (35%) compared to those without dose-capping (24%, P = 0.016). The adjusted odds ratio for dose-capped patients experiencing recurrence was 1.64 compared to uncapped patients (95% CI, 1.10-2.43). Overall, dose-capped patients were less likely to experience significant toxicity requiring dose reduction and/or treatment break when compared to uncapped patients (15% and 28% respectively, P = 0.008).There was significant differences in PFS between capped and uncapped group (77% vs. 85%; P = 0.017). The 5-year OS in the capped group was 75.0%, and 80% in the uncapped group (P = 0.149). CONCLUSIONS: Rectal cancer patients treated with dose-capped CRT were at increased risk of disease recurrence. Patients dosed by actual BSA did experience excessive toxicity compared to dose-capped group. We recommend that chemotherapy dose-capping based on BSA should not be practiced in rectal cancer patients undergoing CRT.

Predictors of adherence to aerobic exercise in rectal cancer patients during and after neoadjuvant chemoradiotherapy.

This pilot study explored predictors of adherence to exercise during and after neoadjuvant chemoradiotherapy (NACRT) in rectal cancer patients. Eighteen rectal cancer patients were prescribed three supervised aerobic exercise sessions/week during NACRT followed by ≥150 min/week of unsupervised aerobic exercise after NACRT. Although not statistically significant, adherence to supervised exercise during NACRT was meaningfully better for patients who were women (d = .82; P = .12), younger (d = -.62; P = .30), married (d = .62; P = .42), with better mental health (r = .32; P = .21), fewer diarrhea symptoms (r = .48; P = .052), and higher anticipated enjoyment (r = .31; P = .23), support (r = .32; P = .22), and motivation (r = .31; P = .23). After NACRT, adherence was significantly better for patients who reported worse mental health (r = -.56; P = .046) and meaningfully better for patients who were women (d = .54; P = .38), better educated (d = .77; P = .22), had no comorbidities (d = -.63; P = .17), and exercised at baseline (d = 1.05; P = .12). Demographics, tumor side effects, and motivational variables may predict adherence to exercise during and after NACRT.

Exercise motivation in rectal cancer patients during and after neoadjuvant chemoradiotherapy.

PURPOSE: Aerobic exercise is safe and feasible for rectal cancer patients during and after neoadjuvant chemoradiotherapy (NACRT), but their motivation to perform such exercise is unknown. Here, we explore the motivational outcomes, perceived benefits and harms, and perceived barriers to exercise during and after NACRT. METHODS: Rectal cancer patients (n = 18) participated in supervised aerobic exercise during NACRT followed by unsupervised exercise after NACRT. Using the theory of planned behavior, we assessed perceived benefits, harms, enjoyment, support, difficulty, and barriers for exercise both during and after NACRT. RESULTS: Patients reported that exercise during NACRT was more enjoyable (p = 0.003) and less difficult (p = 0.037) than initially anticipated. The most common perceived benefits of exercise during NACRT were cardiovascular endurance (75 %), quality of life (75 %), and self-esteem (65 %). After NACRT, the most common perceived benefits were physical functioning (93 %), cardiovascular endurance (86 %), and quality of life (79 %). The most common perceived harms of exercise during NACRT were fatigue (31 %), diarrhea (31 %), and skin irritation (24 %). After NACRT, the most common perceived harms were fatigue (21 %) and hand-foot-syndrome (15 %). Side effects from NACRT were the most common exercise barrier during NACRT (88 %) whereas lack of motivation was the most common barrier after NACRT (79 %). CONCLUSIONS: Rectal cancer patients reported aerobic exercise during NACRT to be more enjoyable and less difficult than anticipated despite significant barriers. This positive motivational response may facilitate recruitment and adherence in future interventions. Moreover, rectal cancer patients identified potential benefits and harms that should be closely monitored in future interventions.

Reasons for delays in diagnosis of anal cancer and the effect on patient satisfaction.

OBJECTIVE: To quantify the time to diagnosis of anal cancer after onset of symptoms, to identify reasons for delays in diagnosis, and to identify the effect of delays on patient satisfaction. DESIGN: Retrospective questionnaire. SETTING: Cross Cancer Institute in Edmonton, Alta. PARTICIPANTS: Patients newly diagnosed with anal cancer on their first visit to the centre. MAIN OUTCOME MEASURES: Timeline from first symptoms to first access to medical care and to diagnosis, and patient satisfaction. RESULTS: Twenty-six patients completed the survey. Although most sought medical attention promptly, 19% waited for more than 6 months. At first visits after symptom onset, a rectal examination was performed in only 54% of patients, a diagnosis of hemorrhoids was given in 27% of patients, and further investigations were ordered in only 54% of patients. If a misdiagnosis of hemorrhoids was made, substantially more visits were required to diagnose the cancer. An average of 3.2 months after the first visit to a physician and 7.4 months after onset of symptoms was needed to obtain a diagnosis. Overall, 28% of patients believed there were no diagnostic delays and 40% of patients thought they were responsible for the delay. Overall, 72% of patients were satisfied with the care they received. Patients who were dissatisfied perceived the delay in diagnosis to be because no action was taken by a physician or the wait was too long for tests or referrals. CONCLUSION: To reduce delays in diagnosis, it might be important to educate relevant populations about symptoms of anal cancer. In addition, primary care physicians must maintain a high index of suspicion of anal cancer in high-risk populations. Finally, there must be a system-wide increase in access to further investigations through gastroenterologists and general surgeons.

A population-based analysis of the impact of 1 vs. 2 doses of mitomycin on patterns of failure of anal cancer patients treated with concurrent chemoradiotherapy.

PURPOSE: We report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM). METHODS: In this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS). RESULTS: 451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc. CONCLUSIONS: Our analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.

The prognostic significance of pretreatment leukocytosis in patients with anal cancer treated with radical chemoradiotherapy or radiotherapy.

BACKGROUND: There are emerging data showing the prognostic significance of pretreatment leukocytosis in patients with cervical cancer; it is generally associated with adverse outcome. However, the prognostic impact of leukocytosis in patients with anal cancer has not been previously reported. OBJECTIVE: The purpose of this study was to assess the relationship between pretreatment leukocytosis and clinical outcomes in patients with anal cancer treated with radical chemoradiotherapy or radiotherapy. DESIGN: This is a retrospective cohort study. SETTING AND PATIENTS: One hundred twenty-six patients with invasive anal canal cancer, treated with radical chemoradiotherapy or radiotherapy between 2000 and 2008 at 2 major tertiary cancer centers, were evaluated. MAIN OUTCOME MEASURES: The primary outcomes were disease-free and overall survival. RESULTS: Median follow-up was 24 months. Pretreatment leukocytosis (white blood cell count >10 × 10/L) was identified in 15.9% (20/126) of patients. After adjusting for sex, tumor size, and stage in a multivariate analysis, leukocytosis remained significantly associated with worse disease-free survival (HR, 2.2; 95% CI, 1.1-4.8; p = 0.045) and worse overall survival (HR, 2.9; 95% CI, 1.1-7.9; p = 0.036). Patients with both leukocytosis and anemia (pretreatment hemoglobin <125 g/L) had the worst prognosis: 2-year disease-free survival 42.1% versus 72.9% for patients without these factors (HR, 2.7; 95% CI, 1.1-6.8; p = 0.033); 2-year overall survival 60.9% versus 89.8% (HR, 4.5; 95% CI, 1.5-13.2; p = 0.006). LIMITATIONS: The study was limited by its retrospective nature and lack of patients with multiple hematologic abnormalities (ie, both anemia and leukocytosis). HIV status was unable to be evaluated. CONCLUSIONS: Pretreatment leukocytosis in patients with anal cancer is associated with significantly worse disease-free and overall survival, which appears to be exacerbated with the presence of pretreatment anemia.

Autotrophic ammonia removal from landfill leachate in anaerobic membrane bioreactor.

Anaerobic ammonium oxidation (ANAMMOX) process, an advanced biological nitrogen removal, removes ammonia using nitrite as the electron acceptor without oxygen. In this paper, ANAMMOX process was adopted for removing NH4+-N from landfill leachate having low COD using anaerobic membrane bioreactor (AnMBR). The AnMBR was optimized for nitrogen loading rate (NLR) varying from 0.025 to 5 kg NH4+-N/m3/d with hydraulic retention time (HRT) ranging from 1 to 3d. NH4+-N removal efficacy of 85.13 +/- 9.67% with the mean nitrogen removal rate of 5.54 +/- 0.63 kg NH4+-N/m3/d was achieved with NLR of 6.51 +/- 0.20kg NH4+-N/m3/d at 1.5 d HRT. The nitrogen transformation intermediates in the form of hydrazine (N2H4) and hydroxylamine (NH2OH) were 0.008 +/- 0.005 and 0.006 +/- 0.001 mg/l, respectively, indicating co-existence of aerobic ammonia oxidizers and ANAMMOX. The free ammonia (NH3) and free nitrous acid (HNO2) concentrations were 26.61 +/- 16.54 mg/l and (1.66 +/- 0.95) x 10(-5) mg/l, preventing NO2(-)-N oxidation to NO3(-)-N enabling sustained NH4+-N removal.

Can radiation restore immunotherapy response in metastatic melanoma refractory to checkpoint inhibitors: An institutional experience in salvaging immunotherapy resistant disease.

Melanoma is an immunogenically active tumor with abundantly expressed lymphoid infiltration. Immunotherapy(IO) has proven as a promising treatment option for melanoma but treatment resistance remains as an issue in the majority of patients.There is emerging evidence that radiotherapy (RT) could modulate the tumor microenvironment, increase antigen presentation, and augment adaptive antitumor immunity. Our objective is to evaluate overall treatment response and safety in patients with metastatic melanoma who progressed while on IO, and were treated with RT concurrently with IO for progressive sites.

Effect of Om chanting and Yoga Nidra on depression anxiety stress, sleep quality and autonomic functions of hypertensive subjects - a randomized controlled trial.

INTRODUCTION: Hypertension (HTN) is a common and growing public health challenge with severe risk factors. Hence, this study aimed to assess the effect of Om chanting and Yoga Nidra on depression, anxiety, stress, sleep quality and autonomic functions on individuals with hypertension. METHODS: This prospective randomized controlled study was conducted in patients with hypertension at Little Flower Medical Research Center. A total of 80 patients with diagnosed hypertension were recruited and randomized equally to either the experimental group or control group. The experimental group received a combination of Om chanting and Yoga Nidra for five days a week for two months. The control group participants continued with their regular conventional medications. Depression anxiety stress scale (DASS), Pittsburgh sleep quality index (PSQI) and heart rate variability (HRV) scores were assessed at baseline, 30 and 60 day for both the groups. RESULTS: A total of 34 subjects in the experimental group and 31 subjects in the control group were included in the analysis. There was a significant (p<0.001) reduction in depression, anxiety, stress, and a significant (p<0.001) improvement in PSQI and HRV parameters in the experimental group was observed as compared to the control group. No adverse events were reported during the trial period. CONCLUSIONS: The current study validates the effectiveness of Om chanting and Yoga Nidra in reducing depression, anxiety, stress and improving sleep quality and autonomic functions in hypertensive patients. These interventions could thus be considered a safer form of complementary therapy in managing stress and hypertension.

Effects of exercise during and after neoadjuvant chemoradiation on symptom burden and quality of life in rectal cancer patients: a phase II randomized controlled trial.

PURPOSE: We previously demonstrated that exercise during and after neoadjuvant chemoradiation (NACRT) for rectal cancer may improve the rate of pathologic complete/near complete response. Here, we report the effects of exercise on symptom management and quality of life (QoL). METHODS: Rectal cancer patients (N = 36) were randomized to a supervised high-intensity interval training program during NACRT followed by unsupervised continuous exercise after NACRT or usual care. Patient-reported outcomes were assessed at baseline, post-NACRT, and presurgery including symptom burden (M.D. Anderson Symptom Inventory) and QoL (European Organisation for Research and Treatment of Cancer QLQ- C30 and -CR29). RESULTS: During NACRT, exercise significantly worsened stool frequency (adjusted between-group difference, 25.8; 95% CI, 4.0 to 47.6; p = 0.022), role functioning (adjusted between-group difference, -21.3; 95% CI, -41.5 to -1.1; p = 0.039), emotional functioning (adjusted between-group difference, -11.7; 95% CI, -22.0 to -1.4; p = 0.028), and cognitive functioning (adjusted between-group difference, -11.6; 95% CI, -19.2 to -4.0; p = 0.004) compared to usual care. After NACRT, exercise significantly worsened diarrhea (adjusted between-group difference, 1.2; 95% CI, 0.1 to 2.3; p = 0.030) and embarrassment (adjusted between-group difference, 19.7; 95% CI, 7.4 to 32.1; p = 0.003) compared to usual care. CONCLUSIONS: Exercise exacerbated some symptoms and worsened QoL during NACRT; however, most negative effects dissipated after NACRT. Larger trials are necessary to confirm these findings. IMPLICATIONS FOR CANCER SURVIVORS: If the clinical benefit of exercise is confirmed, then the modest symptom exacerbation during NACRT may be considered tolerable. However, in the absence of any clinical benefit, exercise may be contraindicated in this clinical setting.

Effects of Exercise on Motivational Outcomes in Rectal Cancer Patients During and After Neoadjuvant Chemoradiation: A Phase II Randomized Controlled Trial.

OBJECTIVES: Understanding exercise motivation in rectal cancer patients during and after neoadjuvant chemoradiation therapy is important to improve adherence and achieve potential benefit. We report the motivational effects of exercise from the Exercise During and After Neoadjuvant Rectal Cancer Treatment trial. DATA SOURCES: We randomized 36 rectal cancer patients to supervised high-intensity interval training during neoadjuvant chemoradiation therapy followed by unsupervised moderate-to-vigorous exercise after therapy, or usual care. Using the theory of planned behavior, we assessed motivation, perceived benefits/harms, and perceived barriers for exercise during and after therapy. Supervised exercise during neoadjuvant chemoradiation therapy was experienced as meaningfully (d≥0.33) more controllable (p=0.08, d=0.60), more enjoyable (p=0.25, d=0.45), and less difficult (p=0.45, d=-0.38) than anticipated. Unsupervised exercise after therapy was experienced as meaningfully more enjoyable (p=0.047, d=0.50) and less difficult (p=0.43, d=-0.36), but also less controllable (p=0.14, d=-0.80) than anticipated. Common self-reported benefits of exercise both during and after neoadjuvant chemoradiation therapy were cardiovascular endurance, physical functioning, and quality of life. Common self-reported harms were exacerbation of treatment side effects. Frequently reported barriers to exercise during therapy were side effects of treatment, whereas exercise barriers after therapy were lack of motivation and lingering side effects. CONCLUSION: Exercise during and after therapy generally had positive effects on exercise motivation, however, perceived harms and barriers related to treatment side effects were identified. IMPLICATIONS FOR NURSING PRACTICE: Nurses can help rectal cancer patients initiate and maintain exercise during and after neoadjuvant chemoradiation by discussing the potential benefits, harms, and barriers to exercise.

Average lifespan shortened due to cancer in selected countries of North America, Europe, Asia and Oceania, 2006 and 2016.

PURPOSE: We applied a novel measure of average lifespan shortened (ALSS) to examine changes in lifespan among patients who died of cancer over a 10-year period from 2006 to 2016 in 20 selected high-income countries from North America, Europe, Asia, and Oceania. METHODS: We retrieved cancer deaths in each country from the World Health Organization mortality database. We calculated ALSS as a ratio of years of life lost to the expected lifespan among patients who died from cancer. RESULTS: Between 2006 and 2016, we observed modest changes in ALSS for overall cancer deaths over the study in many countries. The changes in the ALSS over time due to any cancer ranged between -1.7 and +0.4 percentage points (pps) among men and between -1.9 and +0.6 pps among women. Across countries, overall cancer deaths led to an average loss between 16% and 22% of their lifespan in men, and between 18% and 24% in women. Across cancer sites, patients who died of central nervous system cancers, for instance, lost a large proportion of their lifespan. CONCLUSIONS: In this study, we demonstrated the use of ALSS across selected high-income countries, which enables population-level assessment of premature mortality among cancer patients over time.

Long-Term Patient-Reported Quality of Life of Anal Cancer Survivors Treated With Intensity Modulated Radiation Therapy and Concurrent Chemotherapy: Results From a Prospective Phase II Trial.

PURPOSE: Intensity modulated radiation therapy (IMRT) has confirmed its superiority in improving acute treatment-related toxicities in anal cancer, without compromising tumor control. However, the effect of IMRT on long-term quality of life (QOL) is poorly documented. The study prospectively evaluated the long-term patient-reported QOL after IMRT-based chemoradiation in anal cancer. METHODS AND MATERIALS: Fifty-eight patients treated with IMRT and concurrent 5 fluorouracil/mitomycin-C were enrolled in the study. A prespecified secondary endpoint was prospective evaluation of long-term QOL. Fifty-four patients underwent QOL evaluation at baseline, after treatment, and during follow-up until 60 months, with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scales and the Colorectal Cancer-Specific Quality Of Life Questionnaire (QLQ-CR29) scales. The QOL scores at baseline and posttreatment periods were compared. RESULTS: For QLQ-C30, at 60 months, the mean scores of global health status, all functional scales, and all symptoms except diarrhea had improved, indicating normalization of QOL. Clinically and statistically significant improvements in the global health status (15.4; P = .003), role functioning (19.3; P = .0017), emotional functioning (18.9; P = .008), and social functioning (29.8; P ≤ .001) were observed. Diarrhea persisted as a concern over the years (P = .172). For European Organization for Research and Treatment of Cancer QLQ-CR29, rectal pain (-38.6; P = .001), mucous or blood discharge per rectum (-22.8; P = .005), and perianal soreness (-37.3; P ≤ .001) were improved both clinically and statistically. Clinically significant fecal leakage was reported by 16% of patients (5.6; P = .421). Volumes receiving 45 and 54 Gy were independent predictors for fecal incontinence. Clinically and statistically significant urinary incontinence occurred in 21% of patients (17.5; P = .014). Deterioration of dyspareunia was clinically significant (26.7; P = .099) at 60 months. CONCLUSIONS: Compared with historical data, IMRT is associated with reduced long-term effects on QOL. The majority of patients treated with IMRT experienced clinically significant recovery of function and improvement in QOL over 5 years after completion of treatment. Specific toxicities such as chronic diarrhea, fecal incontinence, and urinary and sexual dysfunction were primarily responsible for deterioration of the long-term QOL. Future research aimed at reducing such toxicities is needed to further improve long-term QOL in anal cancer.

Long-term outcome of breast cancer patients with one to two nodes involved - application of nodal ratio.

Nodal ratio (NR) is defined as the number of involved nodes to the number of nodes examined. There is limited information on the application of NR on population data. Previous reports in breast cancer generally analyzed one to three positive axillary nodes as a single group. This study investigates whether one to three positive axillary nodes is a homogeneous group in prognosis by comparing one to two positive nodes to three positive nodes. The population-based registry of a Canadian province from 1981 through 1995 was searched. As the reliability of nodal assessment depends on the number of nodes sampled, we also studied the subgroup of patients with greater than or equal to eight nodes dissected. Of a total of 5,996 breast cancer patients, 1187 had one to three positive axillary nodes. The 263 patients with three positive nodes compared to the 924 patients with one to two nodes fared worse with a significantly reduced cause-specific survival (CSS) and overall survival (OS). Patients with one to two positive nodes had similar CSS (p=0.31) and OS (p=0.63). Among those with greater than or equal to eight nodes dissected, there were 677 patients with one to two positive nodes. CSS and OS were not significantly different between one versus two positive nodes (p=0.16 and 0.34, respectively), but with NR, the corresponding p values were 0.0068 and 0.08, respectively. The cutoff value of NR 0.15 was found to be most useful and confirmed by the validation dataset. NR is able to segregate patients better than the absolute number of positive nodes used in the current staging system. NR should be incorporated into the staging system.

Outcome analysis of breast cancer patients who declined evidence-based treatment.

BACKGROUND: To analyze the characteristics and outcomes of women with breast cancer in the Northern Alberta Health Region (NAHR) who declined recommended primary standard treatments. METHODS: A chart review was performed of breast cancer patients who refused recommended treatments during the period 1980 to 2006. A matched pair analysis was performed to compare the survival data between those who refused or received standard treatments. RESULTS: A total of 185 (1.2%) patients refused standard treatment. Eighty-seven (47%) were below the age of 75 at diagnosis. The majority of those who refused standard treatments were married (50.6%), 50 years or older (60.9%), and from the urban area (65.5%). The 5-year overall survival rates were 43.2% (95% CI: 32.0 to 54.4%) for those who refused standard treatments and 81.9% (95% CI: 76.9 to 86.9%) for those who received them. The corresponding values for the disease-specific survival were 46.2% (95% CI: 34.9 to 57.6%) vs. 84.7% (95% CI: 80.0 to 89.4%). CONCLUSIONS: Women who declined primary standard treatment had significantly worse survival than those who received standard treatments. There is no evidence to support using Complementary and Alternative Medicine (CAM) as primary cancer treatment.

Chylous ascites in a case of henoch-schonlein purpura - A case report and literature review.

Chylous ascites is a rare form of ascites characterized by the accumulation of lymph fluid in the peritoneal cavity. Henoch-Schonlein purpura (HSP) is a form of vasculitis usually seen in children affecting small vessels. Gastrointestinal (GI) manifestations of HSP are coming to the forefront as a presenting symptom. The presence of a rash usually succeeds the GI manifestations, making diagnosis difficult and leading to unnecessary surgical interventions. Our case shows a 38-year-old female who presented with an acute abdomen followed by an erythematous rash noticed later on, with radiological investigations suggestive of acute appendicitis. Chylous ascites was found as an incidental finding on diagnostic laparoscopy with a healthy appendix.

Résumé L'ascite chyleuse est une forme rare d'ascite caractérisée par l'accumulation de liquide lymphatique dans la cavité péritonéale. Henoch-Schonlein le purpura (HSP) est une forme de vascularite généralement observée chez les enfants et affectant les petits vaisseaux. Les manifestations gastro-intestinales (GI) de la HSP arrivent au premier plan comme symptôme révélateur. La présence d'une éruption cutanée succède généralement aux manifestations gastro-intestinales, rendant le diagnostic difficile et conduisant à des interventions chirurgicales inutiles. Notre cas montre une femme de 38 ans qui s'est présentée avec un abdomen aigu suivi d'un érythémateux éruption cutanée constatée ultérieurement, avec des investigations radiologiques évocatrices d'une appendicite aiguë. Une ascite chyleuse a été découverte de manière fortuite sur laparoscopie diagnostique avec un appendice sain. Mots-clés: Abdomen aigu, ascite chyleuse, purpura Henoch-Schonlein.

The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy.

Background: Programmed death-ligand 1 (PD-L1) expression has been shown to be prognostic in many cancer types and used in consideration of checkpoint inhibitor immunotherapy. However, there are very limited and conflicting data on the prognostic impact of PD-L1 in patients with anal squamous cell carcinoma (ASCC). The objectives of this study were to measure the expression of PD-L1 and CD8 in patients with ASCC treated with radical chemoradiotherapy (CRT) and to correlate tumor expression with progression-free survival (PFS) and overall survival (OS). Methods: Ninety-nine patients with ASCC treated with primary CRT at two tertiary care cancer centers between 2000 and 2013, with available pre-treatment tumors, were included. Tissue microarrays (TMAs) from pre-treatment tumor specimens were stained for PD-L1 and CD8. PD-L1 expression in the tumor and stroma was quantified using HALO image analysis software, and results were interpreted using quantitative methods. The density of CD8 cells within the tumor was interpreted by a trained pathologist semi-quantitatively, using a 0-4 scoring system. Kaplan-Meier analysis with log-rank was used to determine the significance in the association of tumor markers with PFS and OS. Cox multivariate analysis was used to explore independent predictors of PFS and OS. Results: Of the 99 patients, 63 (64%) had sufficient tumor samples available for full analysis. CD8 high status was documented in 32 of 63 (50.8%) % of cases. PD-L1 expression was positive in 88.9% of cases. Approximately half the patients had tumor PD-L1 ≥ 5%. Patients with tumor PD-L1 ≥ 5% had better OS vs those with lower expression, HR=0.32 (95% CI 0.11-0.87), p=0.027; 10 years OS: 84% for tumor PD-L1 ≥ 5% vs 49% for PD-L1 < 5%. PD-L1 expression was not associated with PFS. On multivariate analysis, tumor PD-L1 ≥ 5% showed a trend to statistical significance for better OS, HR=0.55 (95% CI 0.12- 1.00), p=0.052. Conclusions: Tumor PD-L1≥5% is associated with OS in patients with ASCC treated with CRT. PD-L1 expression status using this unique cut-point warrants further validation for prognostication in patients with this disease. Future studies are required to determine the benefit of alternative treatment strategies based on PD-L1 status.