Radiation Therapy for Colorectal Liver Metastasis: The Effect of Radiation Therapy Dose and Chemotherapy on Local Control and Survival.

Purpose: Colorectal liver metastases (CLMs) represent a radioresistant histology. We aimed to investigate CLM radiation therapy (RT) outcomes and explore the association with treatment parameters. Methods and Materials: This retrospective analysis of CLM treated with RT at Memorial Sloan Kettering Cancer Center used Kaplan-Meier analysis to estimate freedom from local progression (FFLP), hepatic progression-free, progression-free, and overall survival (OS). Cox proportional hazards regression was used to evaluate association with clinical factors. Dose-response relationship was further evaluated using a mechanistic tumor control probability (TCP) model. Results: Ninety patients with 122 evaluable CLMs treated 2006 to 2019 with a variety of RT fractionation schemes with a median biologically effective dose (α/ß = 10; BED10) of 97.9 Gy (range, 43.2-187.5 Gy) were included. Median lesion size was 3.5 cm (0.7-11.8 cm). Eighty-seven patients (97%) received prior systemic therapy, and 73 patients (81%) received prior liver-directed therapy. At a median follow-up of 26.4 months, rates of FFLP and OS were 62% (95% CI, 53%-72%) and 75% (66%-84%) at 1 year and 42% (95% CI, 32%-55%) and 44% (95% CI, 34%-57%) at 2 years, respectively. BED10 below 96 Gy and receipt of ≥3 lines of chemotherapy were associated with worse FFLP (hazard ratio [HR], 2.69; 95% CI, 1.54-4.68; P < .001 and HR, 2.67; 95% CI, 1.50-4.74; P < .001, respectively) and OS (HR, 2.35; 95% CI, 1.35-4.09; P = .002 and HR, 4.70; 95% CI, 2.37-9.31; P < .001) on univariate analyses, which remained significant or marginally significant on multivariate analyses. A mechanistic Tumor Control Probability (TCP) model showed a higher 2-Gy equivalent dose needed for local control in patients who had been exposed to ≥ 3 lines of chemotherapy versus 0 to 2 (250 ± 29 vs 185 ± 77 Gy for 70% TCP). Conclusions: In a large single-institution series of heavily pretreated patients with CLM undergoing liver RT, low BED10 and multiple prior lines of systemic therapy were associated with lower local control and OS. These results support continued dose escalation efforts for patients with CLM.

Radiation therapy for de novo anorectal cancer in patients with a history of prostate radiation therapy.

Introduction: Radiation therapy (RT) for anorectal cancer after prior prostate cancer RT is usually avoided due to concern for complications. Data on this topic is scarce. Our aim was to evaluate tolerability, toxicity, and clinical outcomes associated with a second course of pelvic radiation in men with de novo anorectal cancers previously treated with RT for prostate cancer. Materials/methods: We conducted a single-institution retrospective study of men treated with RT for rectal or anal cancer after prior prostate RT. Toxicity data were collected. Treatment plans were extracted to assess doses to organs at risk and target coverage. Cumulative incidence was calculated for local and distant progression. Kaplan-Meier curves were used to estimate overall survival (OS) and progression-free survival (PFS). Results: We identified 26 patients who received anorectal RT after prostate cancer RT: 17 for rectal cancer and 9 for anal cancer. None had metastatic disease. Prior prostate RT was delivered using low dose rate brachytherapy (LDR), external beam RT (EBRT), or EBRT + LDR. RT for rectal cancer was delivered most commonly using 50.4Gy/28 fractions (fr) or 1.5 Gy twice-daily to 30-45 Gy. The most used RT dose for anal cancer was 50Gy/25 fr. Median interval between prostate and anorectal RT was 12.3 years (range:0.5 - 25.3). 65% and 89% of rectal and anal cancer patients received concurrent chemotherapy, respectively. There were no reported ≥Grade 4 acute toxicities. Two patients developed fistulae; one was urinary-cutaneous after prostate LDR and 45Gy/25fr for rectal cancer, and the other was recto-vesicular after prostate LDR and 50Gy/25fr for anal cancer. In 11 patients with available dosimetry, coverage for anorectal cancers was adequate. With a median follow up of 84.4 months, 5-yr local progression and OS were 30% and 31% for rectal cancer, and 35% and 49% for anal cancer patients, respectively. Conclusion: RT for anorectal cancer after prior prostate cancer RT is feasible but should be delivered with caution since it poses a risk of fistulae and possibly bleeding, especially in patients treated with prior LDR brachytherapy. Further studies, perhaps using proton therapy and/or rectal hydrogel spacers, are needed to further decrease toxicity and improve outcomes.

Prospective Clinical Evaluation of Integrating a Radiation Anatomist for Contouring in Routine Radiation Treatment Planning.

Purpose: A radiation anatomist was trained and integrated into clinical practice at a multi-site academic center. The primary objective of this quality improvement study was to determine whether a radiation anatomist improves the quality of organ-at-risk (OAR) contours, and secondarily to determine the impact on efficiency in the treatment planning process. Methods and Materials: From March to August 2020, all patients undergoing computed tomography-based radiation planning at 2 clinics at Memorial Sloan Kettering Cancer Center were assigned using an "every other" process to either (1) OAR contouring by a radiation anatomist (intervention) or (2) contouring by the treating physician (standard of care). Blinded dosimetrists reported OAR contour quality using a 3-point scoring system based on a common clinical trial protocol deviation scale (1, acceptable; 2, minor deviation; and 3, major deviation). Physicians reported time spent contouring for all cases. Analyses included the Fisher exact test and multivariable ordinal logistic regression. Results: There were 249 cases with data available for the primary endpoint (66% response rate). The mean OAR quality rating was 1.1 ± 0.4 for the intervention group and 1.4 ± 0.7 for the standard of care group (P < .001), with subset analysis showing a significant difference for gastrointestinal cases (n = 49; P <.001). Time from simulation to contour approval was reduced from 3 days (interquartile range [IQR], 1-6 days) in the control group to 2 days (IQR, 1-5 days) in the intervention group (P = .007). Both physicians and dosimetrists self-reported decreased time spent contouring in the intervention group compared with the control group, with a decreases of 8 minutes (17%; P < .001) and 5 minutes (50%; P = .002), respectively. Qualitative comments most often indicated edits required to bowel contours (n = 14). Conclusions: These findings support improvements in both OAR contour quality and workflow efficiency with implementation of a radiation anatomist in routine practice. Findings could also inform development of autosegmentation by identifying disease sites and specific OARs contributing to low clinical efficiency. Future research is needed to determine the potential effect of reduced physician time spent contouring OARs on burnout.

Proton Therapy in the Management of Luminal Gastrointestinal Cancers: Esophagus, Stomach, and Anorectum.

While the role of proton therapy in gastric cancer is marginal, its role in esophageal and anorectal cancers is expanding. In esophageal cancer, protons are superior in sparing the organs at risk, as shown by multiple dosimetric studies. Literature is conflicting regarding clinical significance, but the preponderance of evidence suggests that protons yield similar or improved oncologic outcomes to photons at a decreased toxicity cost. Similarly, protons have improved sparing of the organs at risk in anorectal cancers, but clinical data is much more limited to date, and toxicity benefits have not yet been shown clinically. Large, randomized trials are currently underway for both disease sites.

Proton Therapy in the Management of Hepatocellular Carcinoma.

Proton radiation therapy plays a central role in the treatment of hepatocellular carcinoma (HCC). Because of the near-zero exit dose and improved sparing of normal liver parenchyma, protons are being used even in challenging scenarios, including larger or multifocal liver tumors, and those associated with vascular tumor thrombus. There is a mounting level of evidence that suggests that protons are superior to photons in terms of survival and toxicity outcomes, specifically the progression to liver failure. A randomized controlled trial comparing protons to photons is currently underway to verify this hypothesis.

Proton Therapy in the Management of Pancreatic Cancer.

Radiation therapy plays a central role in the treatment of pancreatic cancer. While generally shown to be feasible, proton irradiation, particularly when an ablative dose is planned, remains a challenge, especially due to tumor motion and the proximity to organs at risk, like the stomach, duodenum, and bowel. Clinically, standard doses of proton radiation treatment have not been shown to be statistically different from photon radiation treatment in terms of oncologic outcomes and toxicity rates as per non-randomized comparative studies. Fractionation schedules and concurrent chemotherapy combinations are yet to be optimized for proton therapy and are the subject of ongoing trials.

Factors Associated With Premature Ovarian Insufficiency in Young Women With Locally Advanced Rectal Cancer Treated With Pelvic Radiation Therapy.

PURPOSE: Pelvic radiation therapy (RT) is standard of care for patients with locally advanced rectal cancer (LARC). Premature ovarian insufficiency (POI) in premenopausal women is a possible side effect. The purpose of our study was to evaluate factors associated with POI in women younger than 50 years, treated with pelvic RT for LARC, including those who underwent ovarian transposition (OT). METHODS AND MATERIALS: We retrospectively reviewed the records of women younger than 50 years treated with pelvic RT for LARC at our institution between 2001 and 2019. Clinical and hormonal data were used to determine ovarian function. The ovaries and uterus were contoured and dose volume histograms were generated. Association of clinical and dosimetric factors with POI within 12 months of RT was evaluated using Wilcoxon-rank sum test and Fisher's exact test. RESULTS: We identified 76 premenopausal women at time of RT with median age of 43 years (range, 20-49). Twenty-six women (34%) underwent OT. Neoadjuvant, concurrent, and adjuvant chemotherapy was administered in 56 (74%), 69 (91%), and 26 (34%) women, respectively. Median RT dose was 50 Gy/25 fractions. Among 75 women with 12 months of follow-up, 25% had preservation of ovarian function, all in the OT group. Ovarian function was preserved in 19 (76%) women who underwent OT. The median of ovarian mean dose was 1.7 Gy in the OT group versus 44.8 Gy in the non-OT group (P < .001). OT and age at RT were significantly associated with POI (P < .001). No patient with ovarian mean dose less than 1.36 Gy developed POI. CONCLUSIONS: OT was significantly associated with reduced risk of POI by enabling lower radiation doses to the ovaries. OT should be considered in young patients undergoing pelvic RT. Although there appears to be a significant association between ovarian mean dose and POI, larger studies are needed to find a dosimetric threshold. Our results suggest keeping the dose to the ovaries as low as reasonably achievable in patients who undergo OT and pelvic RT.

Patient Selection for Surgery vs Radiotherapy for Early Stage Oropharyngeal Cancer.

Surgery and radiation therapy are both commonly used in the treatment of early stage (AJCC stages T1-T2 N0-M0) oropharyngeal squamous cell carcinoma (OPSCC). Transoral robotic surgery (TORS) and intensity modulated radiation therapy (IMRT) have been reported to result in similar survival and disease control outcomes. However, their side effect profiles widely differ. Nevertheless, patients who experience the worst side effects and quality of life are the ones who receive the combination of TORS and adjuvant radiation or chemoradiation therapy. Thus, appropriate patient selection for surgery to minimize the need for multimodality therapy is key. We propose, in this paper, the use of sentinel lymph node biopsy in the node negative (N0) neck as a means that is worth exploring for selecting patients to either radiation therapy or surgery. Patients with a positive sentinel lymph node (SLN) would be better directed to upfront radiation. On the contrary, patients with a negative SLN biopsy would be more confidently directed towards TORS and neck dissection alone.

Stereotactic Radiosurgery for Atrioventricular Node Ablation in Swine: A Study on Efficacy and Dosimetric Evaluation of Organs at Risk.

Introduction Stereotactic radiosurgery (SRS) delivered to arrhythmogenic foci within the heart is a promising treatment modality. We dosimetrically evaluated the radiation dose to the organs at risk of four swine that were successfully treated with linear-accelerator-based SRS for atrioventricular (AV) node ablation. Materials and methods Single-chamber pacemakers were implanted in four large white breed swine. Cardiac computed tomography simulation scans were performed to localize the AV node and organs at risk. SRS (35-40 Gy) was delivered to the AV node, and the pigs were followed up with pacemaker interrogations. One-sample t-tests were used to evaluate Dmax of great vessels, esophagus, and chest wall as compared to known normal tissue constraints as per RTOG 0631 and AAPM Task Group 101. Results All pigs had disturbances of AV conduction with progressive transition into complete heart block. Macroscopic and microscopic evaluation showed fibrosis in the AV node but did not reveal any changes in non-nodal cardiac tissue or vessels. The mean Dmax±SD (p-value) of the chest wall (14.7±3.3 (0.02)), esophagus (10.7±1.1 (<0.01)) superior vena cava (3.3±4.1 (<0.01)), right pulmonary artery (16.1±6.4 (<0.01)), right pulmonary vein (15.7± 5 (<0.01)), left pulmonary artery (11.1±1.7 (<0.01)) and left pulmonary vein (14.1±2.6 (<0.01)), and the inferior vena cava (33.68±1.6 (0.026)) were significantly below the normal tissue constraint cutoffs. Mean±SD (p-value) of the ascending aorta (19.4±16.1 (0.12)) was not significantly different than normal tissue constraint cutoffs. One swine model treated at 40 Gy had small area of hotspot in the ascending aorta (40.65 (0.4 cc)). Conclusion We have demonstrated in our swine models that SRS using 35-40 Gy can be done without exceeding known human normal tissue constraints to the chest wall, esophagus, and great vessels.

Ablative radiation therapy for hepatocellular carcinoma is associated with reduced treatment- and tumor-related liver failure and improved survival.

BACKGROUND: More than 70% of patients with hepatocellular carcinoma (HCC) are not candidates for curative therapy or recur after curative-intent therapy. There is growing evidence on the use of ablative radiation therapy (RT) for liver tumors. We aimed to analyze outcomes of HCC patients treated with conventional versus ablative RT. METHODS: We retrospectively analyzed medical records of HCC patients treated with liver RT from 2001 to 2019. We defined ablative RT as biologically effective dose (BED) ≥80 Gy. RECIST 1.1 was used to define early responses at 3-6 months after RT, and local control (LC) at last follow-up (FU). Data was analyzed using Fisher exact test, Kaplan-Meier, cumulative incidence rates, Cox proportional hazards model and Fine-Gray competing risks. RESULTS: Forty-five patients were identified, of whom 14 (31.1%) received ablative RT using a stereotactic technique. With median FU of survivors of 10.1 months, 1-year cumulative incidence of LC was 91.7% for ablative and 75.2% for BED <80 Gy. At early FU, patients treated with ablative RT had better responses compared to BED <80 Gy, with 7% progressing versus 19%, and 21.4% with complete response versus none (P=0.038). On univariate analysis (UVA), Child-Pugh (CP) score [hazard ratio (HR): 3 for CP-B, HR: 16 for CP-C] and BED (HR: 7.69 for BED <80 Gy) correlated with deterioration of liver function, leading to liver failure. Most liver failure cases were due to disease progression. No RT-related liver failure occurred in the ablative RT group. On UVA, only BED ≥80 Gy was associated with improved overall survival (OS) (HR: 0.4; P=0.044). Median OS (mOS) and 1-year OS were 7 months and 35% respectively for BED <80 Gy compared to 28 months and 66% for BED ≥80 Gy. No grade 3+ bowel toxicity was reported in either group. CONCLUSIONS: Greater than 90% LC was achieved after stereotactic ablative RT, which was associated with minimized tumor- and treatment-related liver failure and improved survival for highly selected inoperable HCC patients.

Association of Ablative Radiation Therapy With Survival Among Patients With Inoperable Pancreatic Cancer.

IMPORTANCE: Surgical resection has been considered the only curative option for patients with pancreatic cancer. Nonoperative local treatment options that can provide a similar benefit are needed. Emerging radiation techniques that address organ motion have enabled curative radiation doses to be given in patients with inoperable disease. OBJECTIVE: To determine the association of hypofractionated ablative radiation therapy (A-RT) with survival for patients with locally advanced pancreatic cancer (LAPC) treated with a novel radiation planning and delivery technique. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 119 consecutive patients treated with A-RT between June 2016 and February 2019 and enrolled in a prospectively maintained database. Patients were treated with a standardized technique within a large academic cancer center regional network. All patients with localized, unresectable, or medically inoperable pancreatic cancer with tumors of any size and less than 5 cm luminal abutment with the primary tumor were eligible. INTERVENTIONS: Ablative RT (98 Gy biologically effective dose) was delivered using standard equipment. Respiratory gating, soft tissue image guidance, and selective adaptive planning were used to address organ motion and limit the dose to surrounding luminal organs. MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS). Secondary outcomes included incidence of local progression and progression-free survival. RESULTS: Between 2016 and 2019, 119 patients (59 men, median age 67 years) received A-RT, including 99 with T3/T4 and 53 with node-positive disease, with a median carbohydrate antigen 19-9 (CA19-9) level greater than 167 U/mL. Most (116 [97.5%]) received induction chemotherapy for a median of 4 months (0.5-18.4). Median OS from diagnosis and A-RT were 26.8 and 18.4 months, respectively. Respective 12- and 24-month OS from A-RT were 74% (95% CI, 66%-83%) and 38% (95% CI, 27%-52%). Twelve- and 24-month cumulative incidence of locoregional failure were 17.6% (95% CI, 10.4%-24.9%) and 32.8% (95% CI, 21.6%-44.1%), respectively. Postinduction CA19-9 decline was associated with improved locoregional control and survival. Grade 3 upper gastrointestinal bleeding occurred in 10 patients (8%) with no grade 4 to 5 events. CONCLUSIONS AND RELEVANCE: This cohort study of patients with inoperable LAPC found that A-RT following multiagent induction therapy for LAPC was associated with durable locoregional tumor control and favorable survival. Prospective randomized trials in patients with LAPC are warranted.

Outcomes after radiation therapy for T2N0/stage II glottic squamous cell carcinoma.

BACKGROUND: We report outcomes for patients with T2N0M0 glottic squamous cell carcinoma (SCC) treated with radiation therapy (RT). METHODS: Patients who received definitive RT for T2 glottic SCC from 2000 through 2013 were retrospectively reviewed. RESULTS: One hundred and thirteen patients were analyzed (median follow-up time 91 months; 85 patients received three-dimensional conformal radiotherapy [3D-CRT] and 28 received intensity-modulated radiation therapy [IMRT]). Fractionation was conventional (58%) or altered (42%); 20 patients (18%) received concurrent chemotherapy. Five-year local control was 83% for the 3D-CRT vs 81% for the IMRT group (P = .76). The ultimate locoregional control at 5 years was 100% for IMRT vs 91% for 3D-CRT (P = .1). The 5-year overall survival (OS) was 78% for 3D-CRT vs 81% for IMRT (P = .83). On multivariate analysis, younger age was the only independent predictor of improved OS (P = .0002). CONCLUSIONS: Oncologic and survival outcomes were excellent for patients with T2N0 glottic cancer. Patients treated with IMRT and 3D-CRT had no statistically significant differences in all investigated endpoints.

Demographics and outcomes of meningioma patients treated at a tertiary care center in the Middle East.

OBJECTIVE: Meningioma is the most common intracranial primary brain tumor. Risk factors such as age and exposure to radiation as well as prognostic factors such as grade, location, and extent of surgical resection have been reported in the literature worldwide; however, to our knowledge, data from the Middle East is still warranted. In this study, we aim to identify the characteristics, risk factors and outcomes of meningioma patients treated at a multidisciplinary regional referral center in the Middle East. PATIENTS AND METHODS: This is a retrospective chart review with a prospective follow up of outcomes. It included patients diagnosed with meningioma between January 2005 and December 2015 at the American University of Beirut Medical Center. Patient's demographics, risk factors and outcomes were first retrospectively collected. Then, we conducted phone calls to all included alive patients to update their disease status and outcomes. RESULTS: One-hundred and ninety-five patients were included. 69 % had grade I tumors and around 31 % with grades II and III meningiomas. The means of the overall survival and progression free survival (PFS) were 198 and 126 months, respectively. The residence area (city vs. countryside), occupation, alcohol use, oral contraceptive use, family history of meningioma, previous head trauma, radiation exposure for head/brain imaging, cell phone use, and finally, the tumor Ki-67 protein level did not correlate with the survival outcomes. The meningioma grade and extent of resection were significant predictors of the PFS on the univariate analysis, whereas, in the multivariate analysis only previous radiotherapy was significant in prolonging PFS. CONCLUSION: In our study cohort, that included around 30 % grades II and III tumors, previous radiotherapy use was the only significant prognostic factor for longer PFS in patients diagnosed with meningioma. Future prospective studies should be conducted to evaluate genetic and molecular factors that could possibly be linked to meningioma grade and prognosis in our population of Middle Eastern patients.

Carcinoid Tumor Arising from the Sphenoid Sinus Treated with Definitive Intensity-modulated Radiation Therapy: A Case Report.

Head and neck neuroendocrine tumors (NET) are a rare type of cancer. NET can be classified according to the histopathological features. The typical carcinoid tumor is a well-differentiated tumor that is the least common among other types. Owing to its indolent behavior and variable radiological and pathological features, treatment of carcinoid tumors remains a challenge. We report a case of a 54-year-old man presenting with a non-operable carcinoid tumor arising in the sphenoid sinuses treated with radiotherapy with stable disease control after three years follow-up.

Trastuzumab Emtansine for the Treatment of HER-2 Positive Carcinoma Ex-pleomorphic Adenoma Metastatic to the Brain: A Case Report.

Background: Carcinoma Ex-pleomorphic adenoma is a malignant transformation of the common benign neoplasm of the salivary glands, "pleomorphic adenoma." Only two cases were ever reported with brain metastases, with absence of good evidence guiding management of such cases. Case Presentation: A 61-year-old woman presenting with facial paralysis was found to have carcinoma ex-pleomorphic adenoma of the parotid gland. Twenty months after local treatment, she developed brain metastases, treated with whole brain radiation therapy. The patient then had progressive intracranial disease after the end of radiation therapy in addition to the appearance of liver metastases. Pathology showed overexpression of HER2, so she was treated with Trastuzumab Emtansine (TDM1). Follow-up imaging revealed significant decrease in the number and size of the metastatic brain lesions in keeping with a good response to TDM1 treatment. Conclusion: Prognosis of metastatic carcinoma ex-pleomorphic adenoma is very poor, and there is no clear management for such cases. We present a case of carcinoma ex-pleomorphic adenoma with brain and liver metastases with a very good response to TDM1 treatment.

Increase in spleen volume as a predictor of oxaliplatin toxicity.

BACKGROUND: Oxaliplatin is a nonconventional third-generation platinum compound. It is an important chemotherapeutic agent in regimens used in gastrointestinal carcinomas as well as other malignancies. Oxaliplatin toxicity profile includes neurotoxicity, hepatotoxicity, and splenomegaly. The primary aim of this study was to measure the spleen volume of patients on oxaliplatin therapy before and during chemotherapy to detect any increase in splenic size as a biomarker for early oxaliplatin toxicity. METHODS: This was a prospective pilot study conducted at the American University of Beirut-Medical Center. Fifty patients newly started on oxaliplatin were included. The spleen volume was measured from the patients' baseline CT scan using the IntelliSpace Portal upgraded system (using Response Evaluation Criteria In Solid Tumors [RECIST]), for each follow-up CT scan. Side effects were evaluated at each patient visit and graded according to the severity. RESULTS: Thirty-seven (74%) patients developed an increase in spleen size. Thirty-three (66%) sampled patients developed peripheral neuropathy (all grades) at 3 months, whereas only two (4%) patients developed grade 3 neuropathy. Only one (3%) patient who developed an increase in spleen size also developed grade 3 peripheral neuropathy - a result that is significantly different (p<0.001) when comparing patients with an increase in spleen size who also developed peripheral neuropathy of other grades. CONCLUSION: An increase in spleen volume possibly precedes a significant peripheral neuropathy which could be a potential marker for oxaliplatin-induced toxicity.

Prevalence and Severity of Sleep Disturbances among Patients with Early Breast Cancer.

CONTEXT: Data regarding health-related quality of life in breast cancer patients in the Middle East are limited with fatigue and sleep disturbance being the most distressing symptoms reported by patients treated for early breast cancer. AIMS: The aim of this study was to examine the prevalence and incidence of insomnia among patients with early-stage breast cancer patients treated with chemotherapy. SUBJECTS AND METHODS: This was a prospective cohort study. We enrolled patients with stage I-III breast cancer patients treated with chemotherapy at the American University of Beirut Medical Center. At three different time points (prior to, during, and following chemotherapy), we assessed the severity of sleep disturbances using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. The Institution Review Board approved the study. RESULTS: Fifty-two patients were recruited. There was a significant increase in sleep disturbances during chemotherapy which improved to below baseline levels on completion of therapy. Prior to chemotherapy, 36% of patients reported poor sleep versus 58% during chemotherapy. The percentage of patients reporting clinical insomnia rose from 11% pretreatment to 36% during chemotherapy reflecting a significant symptomatic burden that is poorly documented and managed in routine clinical practice. CONCLUSIONS: Patients with nonmetastatic breast cancer experience an increase in sleep disturbances during the treatment phase. Physicians should be aware of the need to routinely screen for sleep disturbance in breast cancer patients undergoing chemotherapy.

Younger age is an independent predictor of worse prognosis among Lebanese nonmetastatic breast cancer patients: analysis of a prospective cohort.

BACKGROUND: Several retrospective studies have reported that younger age at presentation is associated with a worse prognosis for nonmetastatic breast cancer patients. In this study, we prospectively assessed the association between different baseline characteristics (age, tumor characteristics, mode of treatment, etc) and outcomes among newly diagnosed nonmetastatic Lebanese breast cancer patients. METHODS: We recruited a sample of 123 women newly diagnosed with nonmetastatic breast cancer presenting to American University of Beirut Medical Center. Immunohistochemical, molecular (vitamin D receptor, methylene tetrahydrofolate reductase polymorphisms), and genetic assays were performed. Patient characteristics were compared by age group (<40 and ≥40 years). A Cox regression analysis was performed to evaluate the variables affecting the disease-free survival (DFS). Outcome data were obtained, and DFS was estimated. RESULTS: Among the 123 patients, 47 were 40 years of age or younger, and 76 were older than 40 years. Median follow-up duration was 58 months. Nine out of 47 patients <40 years (19.1%) experienced disease relapse in contrast to four out of 76 patients >40 years (5.2%). A wide immunohistochemical panel included Ki-67, cyclin B1, p53, platelet-derived growth factor receptor, and vascular endothelial growth factor receptor, and did not reveal any significant difference in these markers between the two age groups. Older patients had a larger percentage of Luminal A than younger patients. On multivariate analysis including age, stage, grade, and subtype, only age <40 and stage were significantly associated with shorter DFS with hazard ratios of 4 (p=0.03, 95% confidence interval [CI]: 1.1-13.5) and 3 (p=0.03, 95% CI: 0.8-14.9), respectively. The estimated 5-year DFS for patients >40 years was 90%, and for patients <40 years was 37%. CONCLUSION: Being <40 years old was an independent risk factor for recurrence in this cohort of patients.

Intraoperative Radiation Therapy: A Promising Treatment Modality in Head and Neck Cancer.

Every year, almost 62,000 are diagnosed with a head and neck cancer (HNC) and 13,000 will succumb to their disease. In the primary setting, intraoperative radiation therapy (IORT) can be used as a boost in select patients in order to optimize local control. Addition of external beam radiation to limited volumes results in improved disease control over surgery and IORT alone. In the recurrent setting, IORT can improve outcomes from salvage surgery especially in patients previously treated with external beam radiation. The use of IORT remains limited to select institutions with various modalities being currently employed including orthovoltage, electrons, and high-dose rate brachytherapy. Practically, execution of IORT requires a coordinated effort and careful planning by a multidisciplinary team involving the head and neck surgeon, radiation oncologist, and physicist. The current review summarizes common uses, outcomes, toxicities, and technical aspects of IORT in HNC patients.