Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome.

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age-adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.

Assessing Radiosensitivity of Bladder Cancer in vitro: A 2D vs. 3D Approach.

Background: Bladder cancer is the fourth most commonly diagnosed cancer among males worldwide. Current treatment strategies established for bladder cancer mainly consist of cystectomy yet advances in radiation therapy have pointed to the value of organ-preserving strategies in preserving patients' quality of life. Aim: To study and compare the radiosensitivity in two-dimension (2D) and physiologically-relevant three-dimension (3D) in vitro culture of three human bladder cancer cell lines, RT4, T24, and UM-UC-3. Materials and Methods: Clonogenic assay was performed to assess cells' radiosensitivity in 2D. Employing the 3D Matrigel™-based cultures to enrich for cancer stem cells (CSCs) allowed us to assess the survival of this subpopulation of cells via evaluating the number, i.e., sphere forming unit (SFU), and the sizes of cultured spheres, formed from cells exposed to different radiation doses compared to non-irradiated cells. Results: Irradiating cells with increasing radiation doses revealed highest survival rates with RT4 cells in 2D, followed by T24 and UM-UC-3. In 3D, however, UM-UC-3 cells were shown to be the most radio-resistant as evidenced by the number of spheres formed, yet they displayed the least efficient volume reduction/regression (VR), whilst the volume decreased significantly for both RT4 and T24 cells. Sphere VR and sphere ratio (SR) values were then plotted against each other demonstrating a linear correlation between volume and number with RT4 and UM-UC-3 cell lines, but not T24. Lastly, multiple regression model was employed to evaluate the possibility of obtaining a function combining both 3D parameters, SR and VR, with the surviving fraction (SF) in 2D, and showed a linear regression for T24 cells only, with a correlation coefficient of 0.97 for the combined parameters. Conclusion: We were able to radiobiologically characterize 3 human bladder cancer cell lines showing differential effects of radiation between 2D and 3D culture systems, paving the way for achieving better assessment of radiosensitivity of bladder cancer in vitro.

Predictors of Cardiac Sparing in Deep Inspiration Breath-Hold for Patients With Left Sided Breast Cancer.

Purpose: The purpose of this study was to evaluate patient-related non-dosimetric predictors of cardiac sparing with the use of deep inspiration breath-hold (DIBH) in patients with left-sided breast cancer undergoing irradiation (RT). Materials and Methods: We retrospectively reviewed charts and treatment plans of one-hundred and three patients with left-sided breast cancer. All patients had both free-breathing (FB) and DIBH (with body surface tracking) plans available. (MHD) and V4 (heart volume receiving at least 4 Gy) were extracted from dose volume histograms. Fisher's exact and Chi-square tests were used to identify predictors of reductions in MHD and V4 after DIBH. Results: One-hundred and three patients were identified and most underwent mastectomy. MHD and V4 decreased significantly in DIBH plans (0.74 ± 0.25 Gy vs. 1.72 ± 0.98 Gy, p < 0.0001 for MHD; 4 ± 4.98 cc vs. 20.79 ± 18.2 cc, p < 0.0001 for V4). Body mass index (BMI), smoking and timing of CT simulation (spring/winter vs. summer/fall) were significant predictors of reduction in MHD whereas BMI, field size, chemotherapy, axillary dissection, and timing of CT simulation predicted reduction in V4. On multivariate analysis, BMI, and timing of CT simulation remained significant predictors of the heart-sparing effect of DIBH. Conclusions: In the setting of limited resources, identifying patients who will benefit the most from DIBH is extremely important. Prior studies have identified multiple dosimetric predictors of cardiac sparing and hereby we identified new non-dosimetric factors such as BMI and timing of treatments.

Novel management of ovarian vein thrombosis: A case report.

Ovarian vein thrombosis (OVT) is a rare serious diagnosis especially if extending to inferior vein cava (IVC). We present a case of 36-year- old female who was diagnosed with right OVT reaching the inferior vein cava following a supra-cervical hysterectomy that was performed in the postpartum period due to excessive bleeding from uterine fibroids. Using the new generation anti-coagulant "rivaroxaban" for six months followed by maintenance regimen of aspirin and sulodexide, complete resolution of the clot was noticed without any adverse event while using this regimen. This is the first OVT case which is completely treated with rivaroxaban without any adjunct invasive modality.

Randomized, Prospective, Open-label Phase III Trial Comparing Mebo Ointment With Biafine Cream for the Management of Acute Dermatitis During Radiotherapy for Breast Cancer.

PURPOSE: Acute radiation dermatitis is a common side-effect of radiotherapy in breast cancer and has a profound impact on patients' quality of life, due to pain and discomfort. The aim of this study is to compare the effect of ß-sitosterol (Mebo) ointment to trolamine (Biafine) cream for the prevention and treatment of radiation dermatitis in breast cancer patients receiving adjuvant radiation therapy. MATERIALS AND METHODS: This is a prospective open-label randomized phase III study developed to assess the efficacy of 2 topical agents used for management of acute radiation dermatitis. Female breast cancer patients who needed a course of radiation therapy in our institution were enrolled and randomized into 2 groups 1 with Mebo ointment and 1 with Biafine cream. Both medications were applied twice per day during the whole period of treatment and skin reactions and related symptoms were assessed weekly during the entire course. Grading of skin reactions was done according to the Radiation Therapy Oncology Group grading system. RESULTS: Between September 2015 and May 2017, a total of 161 patients were recruited for this trial. Mean age was similar for both groups (50.19±12.57 vs. 51.73±11.23, respectively, P=0.41). All other patients and treatment characteristics were similar in both groups, except for the use of boost (82.7% in the Biafine group vs. 36.7% in Mebo group, P=0.012). Analysis was done for reactions recorded before the beginning of the boost and for the entire course including the boost. Using univariate and multivariate analysis, there was no significant difference in grades 2 and 3 dermatitis between the 2 groups. However, the incidence of severe pruritus and severe local skin pain were both significantly reduced in the Mebo group (14.1% in Biafine vs. 2.9% in Mebo, P=0.016 for pruritus and 11.5% vs. 1.4%, respectively, P=0.02 for severe pain). CONCLUSIONS: This study showed no difference between Mebo and Biafine in the incidence and severity of breast skin dermatitis during radiation therapy. However, the use of Mebo ointment was associated with decreased severe pruritus and pain which could positively affect patient comfort and quality of life.

CD4-positive lymphoepithelial-like carcinoma: Report of unusual case.

We are reporting an unusual case of lymphoepithelial-like carcinoma (LELC) in an 8-year-old female patient where the tumor cells showed unusual CD4 expression. The lesion was found in the left submandibular neck region, in the vicinity of the submandibular gland. The salivary gland was not infiltrated by the tumor, and the tumor exhibited a classic LELC with single and clusters of tumor cells surrounded by many hematolymphoid cells. The tumor cells revealed strong positivity for Epstein-Bar virus as confirmed by the EBER: Epstein-Barr Virus in situ hybridization (EBER-ISH) method of staining. Interestingly, the tumor cells expressed membranous immunostaining for the T-helper lymphocyte antibody (CD4) in addition to pan-cytokeratin. A brief discussion about this unusual finding is offered. The patient was treated as a case of Epstein-Bar virus-associated nasopharyngeal carcinoma with excellent response.

Collaborative Pediatric Bone Tumor Program to Improve Access to Specialized Care: An Initiative by the Lebanese Children's Oncology Group.

BACKGROUND: Children with malignant bone tumors have average 5-year survival rates of 60% to 70% with current multimodality therapy. Local control modalities aimed at preserving function greatly influence the quality of life of long-term survivors. In developing countries, the limited availability of multidisciplinary care and limited expertise in specialized surgery and pediatric radiation therapy, as well as financial cost, all form barriers to achieving optimal outcomes in this population. METHODS: We describe the establishment of a collaborative pediatric bone tumor program among a group of pediatric oncologists in Lebanon and Syria. This program provides access to specialized local control at a tertiary children's cancer center to pediatric patients with newly diagnosed bone tumors at participating sites. Central review of pathology, staging, and treatment planning is performed in a multidisciplinary tumor board setting. Patients receive chemotherapy at their respective centers on a unified treatment plan. Surgery and/or radiation therapy are performed centrally by specialized staff at the children's cancer center. Cost barriers were resolved through a program development initiative led by St Jude Children's Research Hospital. Once program feasibility was achieved, the Children's Cancer Center of Lebanon Foundation, via fundraising efforts, provided continuation of program-directed funding. RESULTS: Findings over a 3-year period showed the feasibility of this project, with timely local control and protocol adherence at eight collaborating centers. We report success in providing standard-of-care multidisciplinary therapy to this patient population with complex needs and financially challenging surgical procedures. CONCLUSION: This initiative can serve as a model, noting that facilitating access to specialized multidisciplinary care, resolution of financial barriers, and close administrative coordination all greatly contributed to the success of the program.

Wilms tumor: Successes and challenges in management outside of cooperative clinical trials.

OBJECTIVE/BACKGROUND: Management of Wilms tumor (WT) in children depends on a multidisciplinary approach to treatment, and outcomes have significantly improved as reported by cooperative group clinical trials. Here, we review the clinical outcomes of patients with WT and identify challenges and barriers encountered in multidisciplinary management outside of cooperative clinical trials. METHODS: We retrospectively reviewed the clinical records of 35 children with WT treated between April 2002 and June 2013 at the Children's Cancer Institute in Lebanon. RESULTS: Upfront resection was performed in 23 cases. Biopsies were performed for Stage V tumors (n=4), those with unresectable tumors or inferior vena caval thrombus (n=5), and patients who had partial surgery performed elsewhere prior to presentation (n=2). One patient died due to toxicity prior to surgery. The tumor was Stage I in eight patients, Stage II in five patients, Stages III and IV in nine patients each, and bilateral (Stage V) in four patients. Adherence to The National Wilms Tumor Study-5 recommendations was adequate. At the time of analysis, 30 patients were free of disease and four patients had relapse-all having metastatic disease initially. CONCLUSION: The National Wilms Tumor Study-5 therapy resulted in favorable outcomes in children with nonmetastatic Wilms tumor in the setting of a multidisciplinary approach to therapy and resolution of financial barriers to medical care. Upstaging due to prior intervention and lung radiation therapy to all those with computed tomography-detected lung nodules may both have resulted in overtreatment of a subset of patients. Finally, the relatively high incidence of bilateral tumors suggests the need for further genetic and molecular studies in this patient population.

Global Practice and Efficiency of Multidisciplinary Tumor Boards: Results of an American Society of Clinical Oncology International Survey.

PURPOSE: Multidisciplinary tumor boards (MDTBs) are universally recommended, but recent literature has challenged their efficiency. METHODS: The American Society of Clinical Oncology (ASCO) conducted a survey of a randomly selected cohort of international ASCO members. The survey was built on SurveyMonkey and was sent via e-mail to a sample of 5,357 members. RESULTS: In all, 501 ASCO members practicing outside the United States responded, and 86% of them participated in MDTBs at their own institutions. Those who attended represented a variety of disciplines in 70% to 86% of all MDTBs. The majority of MDTBs held weekly specialty and/or general meetings. Eighty-nine percent of 409 respondents attended for advice on treatment decisions. Survey respondents reported changes of 1% to 25% in treatment plans for 44% to 49% of patients with breast cancer and in 47% to 50% of patients with colorectal cancer. They reported 25% to 50% changes in surgery type and/or treatment plans for 14% to 21% of patients with breast cancer and 12% to 18% of patients with colorectal cancer. Of the 430 respondents 96% said overall benefit to patients was worth the time and effort spent at MDTBs, and 96% said that MDTBs have teaching value. Mini tumor boards held with whatever types of specialists were available were considered valid. In all, 94.8% (425 of 448) said that MDTBs should be required in institutions in which patients with cancer are treated. CONCLUSION: MDTBs are commonplace worldwide. A majority of respondents attend them to obtain recommendations, and they report changes in patient management. Change occurred more frequently with nonmedical oncologists and with physicians who had less than 15 years in practice. MDTBs helped practitioners make management decisions. Mini tumor boards may improve time efficiency and are favored when the full team is not available. Suggestions for improving MDTBs included making them more efficient, better selection and preparation of cases, choosing an effective team leader, and improving how time is used, but more research is needed on ways to improve the efficiency of MDTBs.

Evaluation of chromogenic medium and direct latex agglutination test for detection of group B streptococcus in vaginal specimens from pregnant women in Lebanon and Kuwait.

This study was undertaken to evaluate chromogenic medium and a direct latex agglutination test (DLA) for detection of Group B Streptococcus (GBS) in the vaginal specimens of pregnant women, and to ascertain the prevalence of GBS in this population in Kuwait and Lebanon. Vaginal swabs, collected from women at 35-37 weeks of gestation, were cultured on 5 % sheep blood agar (SBA), colistin nalidixic acid agar (CNA), Strept B Select chromogenic agar (SBS) as well as Lim enrichment broth in 168 cases in Lebanon while only SBA was used for 1391 samples in Kuwait. In addition, vaginal samples from 102 GBS-positive and 20 GBS-negative women near the time of delivery were collected in Kuwait for evaluation of the DLA test. During the study period, the prevalence of GBS colonization was determined to be 20.7 % (288/1391) in Kuwait while 18.4 % (31) of 168 pregnant women in Lebanon had vaginal cultures positive for GBS. By direct plating of vaginal swabs on the three media used, the isolation rates of GBS were 51.6, 64.5 and 77.4 % on SBA, CNA and SBS, respectively, which increased to 90.35, 93.1 and 96.8 %, respectively, following subculture in Lim broth after 18 h of incubation. The sensitivity of the DLA test was found to be dependent on the density of GBS colonization, resulting in 100 % sensitivity and 100 % specificity for heavy (>10(2) c.f.u. per swab) and moderately heavy (50-100 c.f.u. per swab) growth of GBS. However, for vaginal specimens yielding <50 c.f.u. per swab, the sensitivity, specificity, positive and negative predictive values of the DLA test were 100, 55.5, 63.6 and 100 %, respectively. In conclusion, a chromogenic agar, such as SBS, and a DLA test can be used for rapid detection of GBS in pregnant women. The DLA test, in particular, could prove to be a useful tool for immediate detection of GBS in women near delivery so that intrapartum antibiotic prophylaxis can be initiated.

Outcome of Breast Cancer Patients Treated outside of Clinical Trials.

BACKGROUND: Information on outcome of breast cancer patients treated in the community is scarce. Data on outcome of patients treated in real-life clinical practice may provide useful information for performance improvement. METHODS: Study population is from a single institution practice at the American University of Beirut Medical Center. Demographics, clinical characteristics and survival data on patients diagnosed 1997-2010 in two IRB-approved studies were entered and analyzed on SPSS program. Survival was estimated using Kaplan Meier Method. FINDINGS: Total was 519 patients. 23.9% had stage I, 39.7% stage II, 30.4% Stage III and 6% stage IV. ER positive in 74.4% of patients. 30.6% of patients <35 had TNBC compared to 12.3% for the whole group. 45.9% of non-metastatic patients had breast-conserving therapy (BCT). BCT rates increased to 64% during the second half of the study, coinciding with increasing awareness and changing cultural mores. 5-year and 10-year overall survivals for stage I were 98.9% and 80.5%, 89.2% and 70.7% for stage II, 67.6% and 35.5% for stage III, and 39.1% and 26.1% for stage IV respectively. INTERPRETATION: Patients treated outside clinical trials in a multidisciplinary fashion according to guidelines have comparable, and at times better, survival compared to data from trials or population statistics. Locally generated outcome data could be valuable for evaluating results of treatment at individual practices for the purpose of quality assessment and improvement. Our data also provides report of increased rate of breast conserving surgery from Middle East.

Outcome of Ewing sarcoma in a multidisciplinary setting in Lebanon.

Treatment of Ewing sarcoma (ES) necessitates coordinated multi-disciplinary care. We analyzed outcome for 39 patients treated at a single institution in Lebanon, a developing country with available multidisciplinary treatment modalities, where financial barriers to care are overcome by a fundraising system. Median follow-up was 58 months. Five-year overall and event-free survival were 76% and 58%, respectively, for localized disease, and 40% and 38%, respectively, for metastatic disease. We conclude that, in a country with emerging economy, by following international protocols and ensuring availability of needed resources, outcome of patients with ES is similar to that in developed countries.

Cyclophosphamide and topotecan as first-line salvage therapy in patients with relapsed ewing sarcoma at a single institution.

The combination of cyclophosphamide and topotecan (cyclo/topo) has shown objective responses in relapsed Ewing sarcoma, but the response duration is not well documented. We reviewed characteristics and outcome of 14 patients with Ewing sarcoma, treated uniformly at a single institution and offered cyclo/topo at first relapse. Six patients (43%) had relapse at distant sites. All patients received first-line salvage therapy with cyclophosphamide 250 mg/m and topotecan 0.75 mg/m, daily for 5 days repeated every 21 days. The median number of cycles was 4 (range 1 to 10). All toxicities were manageable, the most common being transient cytopenias. There were also 4 episodes of febrile neutropenia, and 3 episodes of gross hematuria. Response was assessable in 13 patients and showed progressive disease in 6 (46%), stable disease in 4 (31%), and partial response in 3 (23%). Nine patients had local control, consisting of radical surgery in 2, radiation in 3, and a combination in 4 patients. Response, when it occurred, was maintained for a median of 8 months (range, 4 to 28 mo). Four patients (29%) are alive at 3, 7, 9, and 110 months after relapse; 1 is receiving cyclo/topo, 1 is on third-line therapy, and 2 are in second and fourth remission. The low toxicity of this combination, and the lack of sustained responses, warrant its investigation in combination with targeted or novel therapeutic agents in relapsed disease.

Rhabdomyosarcoma treatment and outcome at a multidisciplinary pediatric cancer center in Lebanon.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Outcome of patients treated on standard protocols, in a multidisciplinary cancer center setting outside of clinical trials, is not well reported. We reviewed characteristics and outcome of 23 pediatric patients treated at a single, multidisciplinary cancer center in Lebanon, between April 2002 and December 2010. Median follow-up was 41 months. The most commonly affected primary site was the head and neck (48%, n = 11). Nineteen tumors (82.6%) were of embryonal histology. Tumor size was ≥5 cm in eight (34.8%) patients. Sixteen patients (69.6%) had localized disease, and one (4.4%) had metastatic disease. Fifteen (65.2%) had Group III tumors. All patients received chemotherapy, for a duration ranging 21-51 weeks. Upfront surgical resection was performed in 10 patients (43.5%). Eighteen patients (78.3%) received radiation therapy. The 5-year overall and disease-free survival rates were 83% and 64%, respectively. Relapse correlated with absence of surgery. Treatment of childhood RMS in a multidisciplinary cancer center in Lebanon results in similar survival to that in developed countries when similar protocols are applied. There was a higher incidence of local relapse, but those were salvageable with further therapy and surgical local control.

Survey of utilization of multidisciplinary management tumor boards in Arab countries.

Multidisciplinary management (MDM) of cancer patients provides better care and is recommended by all authorities and published guidelines. There is very little documentation of MDM practices in low and middle income countries. A survey of 338 practicing oncology specialists from various Arab countries was conducted at four major pan-Arab oncology conferences in the first half of 2010. While 72% of respondents reported having an MDM tumor board, only 49% reported that their tumor boards met on a weekly basis. Of those who do not have a tumor board, 57% attend a tumor board meeting at another hospital within their country. 60% of respondents attend tumor board meetings to seek group opinion and help in the management of their patients. 93% of physicians surveyed agreed that tumor boards should be mandatory. The vast majority of physicians agreed that in the absence of all specialties, "mini tumor boards" should be organized between available specialists at all hospitals that treat cancer patients.

Vocal changes following radiotherapy to the head and neck for non-laryngeal tumors.

To investigate vocal changes in patients following the neck irradiation for non-laryngeal tumors sparing the glottic region. Fifteen patients were enrolled for the study. Phonatory effort and voice evaluation were reported. Perceptual evaluation and acoustic analysis were performed. Men/women ratio was 6/9. The mean age was 54 years with a range from 24 to 84. The most common primary site of tumor was the nasopharynx and tongue. The mean phonatory effort was significantly greater in the irradiated group versus controls (0.54 vs. 0.08 with a P value 0.01). Fifteen percent reported their voice as being poor and almost 85% as being fair. All the parameters of the GRABS perceptual evaluation were significantly worse in the irradiated group. There were no statistically significant differences between all the acoustic variables in both groups except for an decrease in the Habitual pitch in the irradiated patients. Radiation therapy to head and neck region can affect voice even if the radiation beams spare the vocal folds.

Trends in epidemiology and management of breast cancer in developing Arab countries: a literature and registry analysis.

BACKGROUND: Registries and research on breast cancer in Arabic and developing countries are limited. METHODS: We searched PubMed, Medline, WHO and IAEA publications, national, regional, hospital tumor registries and abstracts. We reviewed and analyzed available data on epidemiological trends and management of breast cancer in Arab countries, and compared it to current international standards of early detection, surgery and radiation therapy. RESULTS: Breast cancer constitutes 13-35% of all female cancers. Almost half of patients are below 50 and median age is 49-52 years as compared to 63 in industrialized nations. A recent rise of Age-Standardized Incidence Rates (ASR) is noted. Advanced disease remains very common in Egypt, Tunisia, Saudi Arabia, Syria, Palestinians and others. Mastectomy is still performed in more than 80% of women with breast cancer. There are only 84 radiation therapy centers, 256 radiation oncologists and 473 radiation technologists in all Arab countries, as compared with 1875, 3068 and 5155, respectively, in the USA, which has an equivalent population of about 300 million. Population-based screening is rarely practiced. Results from recent campaigns and studies show a positive impact of clinical breast examination leading to more early diagnosis and breast-conserving surgery. CONCLUSIONS: Breast cancer is the most common cancer among women in Arab countries with a young age of around 50 years at presentation. Locally advanced disease is very common and total mastectomy is the most commonly performed surgery. Awareness campaigns and value of clinical breast examination were validated in the Cairo Breast Cancer Screening Trial. More radiation centers and early detection would optimize care and reduce the currently high rate of total mastectomies. Population-based screening in those countries with affluent resources and accessible care should be implemented.

Breast cancer patients with 10 or more involved axillary lymph nodes treated by multimodality therapy: influence of clinical presentation on outcome.

PURPOSE: To analyze tumor control and survival for breast cancer patients with 10 or more positive lymph nodes without systemic disease, treated by adjuvant radiation alone or combined-modality therapy. METHODS AND MATERIALS: We reviewed the records of 309 consecutive patients with these characteristics who received locoregional radiotherapy (RT) at our institution. The majority of patients had clinical Stage II or IIIA-B disease (43% and 48%, respectively). The median number of positive axillary lymph nodes was 15 (range, 10-78). Adjuvant therapy consisted of RT alone, with or without chemotherapy, tamoxifen, and/or ovarian castration. RESULTS: The overall 5-year and 10-year disease-free survival (DFS) rates were 20% and 7%, respectively. Median DFS was higher for patients with Stage I-II compared with those with Stage IIIABC (28 vs. 19 months; p = 0.006). Median DFS for patients aged