Early-Onset Colorectal Cancer in Egypt: Pathological Characters, Patterns of Care, and Survival Compared to Average-Age Onset Colorectal Cancer: A Retrospective Multicenter Study.

PURPOSE: Early-onset colorectal cancer (EOCRC) is a rising health problem. The incidence of EOCRC has increased over the past 2 decades all over the world. Reports from Egypt since the 1990s have reported a higher incidence among young populations with no identifiable risk factors. The aim of this study was to assess EOCRC in Egypt regarding incidence, characteristics, treatment pattern, and survival compared with average age onset and elderly patients. MATERIALS AND METHODS: This was a retrospective, record-based, cohort study combining data from four different cancer centers in Egypt. We grouped patients according to age into three categories: the EOCRC group for patients age ≤45 years and the average age onset and elderly cancer group (for patients age ≥65 years). RESULTS: The study included 1,310 patients with histopathologically proven colorectal cancer, representing four different geographical areas in Egypt. Patients with EOCRC represented 42.4% of the study population. Female patients were 50.6% among the EOCRC group and 52.5% among the average age group. Rectal tumors were significantly higher in EOCRC (54.7% v 40.6%; P < .001). There was no significant difference between both groups regarding the tumor stage at presentation, obstruction, or presence of metastases at presentation. Patients with EOCRC had a significantly higher rate of peritoneum/adnexa metastases than the average age ones (12.3% in EOCRC v 6.9% in the average age group; P < .001). No statistically significant differences between EOCRC and average age groups in both disease-free survival and overall survival were reported. CONCLUSION: A comprehensive framework for the study of EOCRC is required in Egypt as well as a genomic analysis to identify possible underlying genetic alterations responsible for the high incidence of EOCRC.

Real-world treatment patterns and clinical outcomes in patients with stage III non-small cell lung cancer: results of KINDLE-Egypt cohort.

Background: Stage III non-small cell lung cancer (NSCLC) being highly heterogeneous requires multimodal therapeutic strategies for optimal management. We present findings on treatment patterns and their associated survival outcomes in patients with stage III NSCLC from the Egypt subset of the KINDLE global real-world study conducted across countries from Asia, Middle East, Africa, and Latin America. Method: Retrospective data from the Egypt subset (21 centers) of adult patients diagnosed with stage III NSCLC between January 2013 and December 2017 were analyzed. Descriptive and inferential statistics summarized treatment modalities, progression-free survival (PFS), and overall survival (OS). Results: Of 421 patients enrolled (median age: 59.0 years), 77.9% were males, 53.5% had stage IIIA disease, 60.8% had adenocarcinoma, 78.4% had an unresectable disease, and 81.5% had Eastern Cooperative Oncology Group performance status ⩽1. Overall, chemotherapy alone (40.4%) was predominantly used in the initial line, whereas definite radiotherapy was used in only 5.0% of patients. In resectable patients, chemotherapy plus surgery (33.8%), surgery alone (20.6%), or other surgery (20.6%) were the top three modalities used in initial line of treatment. Chemotherapy alone was most preferred (48.8%) in unresectable patients, followed by sequential chemoradiotherapy (CRT) (17.6%) and concurrent CRT (9.3%). The overall median PFS was 10.3 months [95% confidence interval (CI), 9.43-12.02], whereas the median OS was 18.5 months (95% CI, 16.46-21.88). Overall, female gender, adenocarcinoma histology, and radical therapy as surgery or CRT predicted significantly longer OS (all p < 0.05). Conclusion: KINDLE-Egypt cohort revealed wide heterogeneities in the treatment patterns of stage III NSCLC. Although deemed resectable, few patients did not undergo surgery, probably due to high smoking rates leading to poor lung function. Lower survival outcomes than other published real-world studies highlight the need for timely approval and availability of novel targeted and immunotherapies to enhance patient outcomes. Trial registration: NCT03725475.

Impact of Extended Adjuvant Temozolamide Beyond 6 Months in the Management of Glioblastoma Patients.

OBJECTIVES: Our study aimed to assess the benefit of prolonging adjuvant temozolomide (TMZ) therapy beyond 6 cycles in glioblastoma multiform patients. MATERIALS AND METHODS: The medical records of 329 patients in 2 cancer centers in Egypt were reviewed from January 2008 to December 2018 who were diagnosed with diffuse gliomas. Data were collected on patient demographics, presenting complaints, tumor size, treatment modalities (extent of surgery, radiotherapy dose and technique, concomitant TMZ, and the number of adjuvant TMZ cycles), and reported adverse events. RESULTS: In the studied cohort, 105 patients were treated with adjuvant TMZ, 33 patients received <6 cycles (TMZL), 41 patients received the standard 6 cycles (TMZS), and 31 patients received >6 cycles (TMZE). Our results showed the median overall survival in the TMZL arm was 8.47 months compared with 15.83 months in the TMZS arm and 27.33 months in the TMZE arm ( P < 0.001). Furthermore, a median progression-free survival of 6.35 months was reported in the TMZL group versus, 12.7 and 22.90 months in (TMZS) and (TMZE) groups, respectively( P < 0.001). In the multivariate analysis, the extended adjuvant TMZ with a hazard ratio of 3.106 (95% CI: 2.43-14.46; P < 0.001) was statistically significantly associated with a better outcome. CONCLUSIONS: Extended adjuvant TMZ therapy beyond 6 cycles may significantly improve the progression-free survival and overall survival in patients with glioblastoma multiform.

Impact of Adjuvant Radiotherapy in Patients with Central Neurocytoma: A Multicentric International Analysis.

BACKGROUND: Central neurocytoma (CN) is a rare tumor accounting for <0.5% of all intracranial tumors. Surgery ± radiotherapy is the mainstay treatment. This international multicentric study aims to evaluate the outcomes of CNs patients after multimodal therapies and identify predictive factors. PATIENTS AND METHODS: We retrospectively identified 33 patients with CN treated between 2005 and 2019. Treatment characteristics and outcomes were assessed. RESULTS: All patients with CN underwent surgical resection. Radiotherapy was delivered in 19 patients. The median radiation dose was 54 Gy (range, 50-60 Gy). The median follow-up time was 56 months. The 5-year OS and 5-year PFS were 90% and 76%, respectively. Patients who received radiotherapy had a significantly longer PFS than patients without RT (p = 0.004) and a trend towards longer OS. In addition, complete response after treatments was associated with longer PFS (p = 0.07). CONCLUSIONS: Using RT seems to be associated with longer survival rates with an acceptable toxicity profile.

Validation of a biomarker tool capable of measuring the absorbed dose soon after exposure to ionizing radiation.

A radiological or nuclear attack could involve such a large number of subjects as to overwhelm the emergency facilities in charge. Resources should therefore be focused on those subjects needing immediate medical attention and care. In such a scenario, for the triage management by first responders, it is necessary to count on efficient biological dosimetry tools capable of early detection of the absorbed dose. At present the validated assays for measuring the absorbed dose are dicentric chromosomes and micronuclei counts, which require more than 2-3 days to obtain results. To overcome this limitation the NATO SPS Programme funded an Italian-Egyptian collaborative project aimed at validating a fast, accurate and feasible tool for assessing the absorbed dose early after radiation exposure. Biomarkers as complete blood cell counts, DNA breaks and radio-inducible proteins were investigated on blood samples collected before and 3 h after the first fraction of radiotherapy in patients treated in specific target areas with doses/fraction of about: 2, 3.5 or > 5 Gy and compared with the reference micronuclei count. Based on univariate and multivariate multiple linear regression correlation, our results identify five early biomarkers potentially useful for detecting the extent of the absorbed dose 3 h after the exposure.

Volumetric-Modulated Arc Radiotherapy with Daily Image-Guidance Carries Better Toxicity Profile for Higher Risk Prostate Cancer.

PURPOSE: To compare radiotherapy-induced toxicity for localized prostate-cancer (PCa) treated with versus without daily image-guidance. PATIENTS AND METHODS: We identified consecutive intermediate and high-risk localized PCa patients treated with definitive radiotherapy using intensity-modulated radiotherapy (IMRT) with variable duration of androgen-deprivation therapy (ADT) within 2015-2016 (Arm-A) and 2005-2007 (Arm-B). Arm-A cases received daily online imaging guidance (IGRT) using cone-beam computed tomography (CBCT) unlike Arm-B candidates with no daily IGRT. After reporting demographic, clinico-pathological features and treatment details, we compared acute (within 3 months post-therapy) and late RT-induced toxicities between study groups graded by RTOG/CTCAE criteria. Uni/multivariate analyses (UVA/MVA) were performed to identify independent predictors for RT-related side-effects. RESULTS: We were able to identify 257 cases who met our inclusion criteria. Overall, median age was 73 years (48-85), 67% had intermediate-risk and 47% received ADT. Arm-A included 72 patients who received IMRT delivered using volumetric-modulated arc therapy (VMAT), whereas, Arm-B was formed of 185 cases who utilized step-and-shoot static IMRT. Clinico-pathological features and treatment details were non-different across study arms except that Arm-A had more Grade Group 3, higher median total dose (79.2 vs. 74 Gy) and more pelvic lymph-nodes RT (p <0.05). Although acute toxicity was similar across groups, Arm-B encountered higher late toxicity score, more intense late genitourinary side-effects (P=0.008), with non-different late lower-gastrointestinal toxicities. On MVA, lack of daily CBCT, African-American race and higher comorbidities were independently predictive for late toxicities.  Conclusion: IMRT with daily CBCT permitted safe delivery of dose-escalated IMRT with improved toxicity profile for higher-risk prostate cancer.

Impact of Adjuvant Radiation Therapy in Patients With Male Breast Cancer: A Multicenter International Analysis.

PURPOSE: Breast cancer in men accounts for approximately 1% of all breast cancers. Breast cancer trials have routinely excluded men. The aim of this analysis was to determine the effect of different treatment factors, in particular, postoperative radiation therapy (RT) on long-term outcomes. METHODS AND MATERIALS: Seventy-one patients with male breast cancer treated in 5 closely cooperating institutions between 2003 and 2019 were analyzed. RESULTS: Almost all patients (95%) underwent surgical resection. Forty-two patients (59%) received chemotherapy, and 59 (83%) received adjuvant hormonal therapy. Of the 71 patients, 52 (73%) were treated with RT. The rate of recurrence was 20% in the whole cohort, with a locoregional recurrence rate of 3%. In the entire group, the 5-year local control (LC) was 95%, whereas 5-year progression-free survival (PFS) and 5-year overall survival (OS) were 62% and 96%, respectively. There was a lower rate of relapses after adjuvant RT (19% vs 32%, P = .05) without in-field relapse after postoperative RT (0%) versus 10% in patients without RT (P = .02). In the multivariate analysis performed, hormonal therapy administration was found to have a possible significant effect on LC and PFS. Administration of adjuvant RT and stage affect PFS. In patients who received RT, there were no grade 3 or 4 acute toxicities. CONCLUSIONS: Adjuvant RT is an effective and safe treatment for male breast cancer patients with no infield relapses and better PFS. Hormonal therapy administration was found to have a possible effect on LC and PFS.

Charlson Comorbidity score influence on prostate cancer survival and radiation-related toxicity.

INTRODUCTION: In addition to survival endpoints, we explored the impact of Charlson Comorbidity-Index (CCI) on the acute and late toxicities in men with localized prostate cancer who received dose-escalated definitive radiotherapy (RT). MATERIALS AND METHODS: CCI scores at diagnosis and survival outcomes were identified for men with intermediate/high-risk prostate cancer treated with RT (1/2007-12/2012). Study-cohort was accordingly grouped into no, mild and severe comorbidity (CCI-0, 1 or 2+). CCI-groups were compared for demographics, prognostic-factors; and RT-related toxicities based on RTOG/CTCAE criteria. Kaplan-Meier curves and Uni/multivariate (MVA) analyses were used to examine the influence of CCI-group on overall (OS), disease-specific (DSS) and biochemical-relapse free (BRFS) survival. RESULTS: We included 257 patients with median age 73 years (48-85), 53% African-American and 67% had intermediate-risk. Median prostate RT-dose was 76 Gy; and 47% received androgen-deprivation therapy. CCI-0,1,2+ groups encompassed 76 (30%), 54 (21%) and 127 (49%) patients, respectively and were well-balanced. Ten and 15-years OS were significantly different (76% versus 46% versus 55% for 10-years OS and 53% versus 31% versus 14% for 15-years OS for CCI-0 versus CCI-1[HR:2.25; CI[1.31-3.87]] versus CCI-2+[HR:2.73; CI[1.73-4.31]]; p < 0.001. CCI-0 had better DSS than CCI-2+ (HR:2.23; CI[1.06-4.68]; p = 0.03) and BRFS was similar (p = 0.99). Late G2/3 RT-toxicities were more common in CCI-2+ (47%) than CCI-1 (44%) and CCI-0 (29%), p = 0.032; with non-different acute-toxicities (p = 0.62). On MVA, increased CCI was deterministic for OS (HR:3.65; CI [1.71:7.79]; p < 0.001) and was only marginal for DSS (HR:2.55; CI [0.98-6.6]; p = 0.05) with no impact on BRFS (p > 0.05). CONCLUSIONS: Higher CCI is a significant predictor for late RT-related side-effects and shorter OS in men with localized prostate cancer. Baseline comorbidities should be considered during initial counseling and follow up visits.

Maximizing the Clinical Benefit of Radiotherapy in Solitary Plasmacytoma: An International Multicenter Analysis.

Objective: Although local definitive radiotherapy (RT) is considered the standard of care for solitary plasmacytoma (SP), the optimal RT parameters for SP patients have not been defined. The aim of this retrospective study is to analyze the effectiveness of various RT doses, volumes, and techniques, as well as to define the relevant prognostic factors in SP. Methods: Between 2000 and 2019, 84 patients, including 54 with solitary bone plasmacytoma (SBP) and 30 with extramedullary plasmacytoma (EMP), underwent RT at six institutions. Results: The overall RT median dose was 42 Gy (range, 36.0-59.4). The median follow-up period was 46 months. Overall, the local control (LC) rate was 96%, while the complete remission (CR) rate was 46%. The 5-year local relapse-free survival (LRFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS), and overall survival (OS) rates were 89%, 71%, 55%, and 93%, respectively. Using an RT dose above 40 Gy was associated with a higher complete remission (CR) rate and a lower rate of local relapse. Modern irradiation techniques were associated with a trend toward a higher LC rate (98% vs. 87% for conventional, p = 0.09) and a significantly lower local relapse rate (6% vs. 25% for conventional, p = 0.04). However, RT dose escalation and technique did not lead to a significant effect on MMFS, PFS, and OS. Univariate analyses identified several patient characteristics as potentially relevant prognostic factors. In SBP patients, systemic therapy administration was associated significantly with MMFS and PFS rates. Conclusion: Using an RT dose >40 Gy and modern RT techniques may improve the local control and reduce the rate of relapse, without a significant impact on survival rates. The addition of systemic therapies may improve the MMFS and PFS rates of SBP patients.

Concomitant Chemoradiotherapy With Image-guided Pulsed Dose Rate Brachytherapy as a Definitive Treatment Modality for Early-stage Cervical Cancer.

PURPOSE: Concurrent chemoradiotherapy (CRT) is the standard of care for patients with bulky cervical cancer. This study aimed to determine the feasibility, tolerance, and effectiveness of pulsed dose rate (PDR) image-guided brachytherapy (IGBT), utilizing magnetic resonance imaging (MRI) planning after CRT for stages IB2 and II cervix cancer patients. METHODS AND MATERIALS: This study planned to include patients with histologically confirmed stage IB2 and II cervical cancer who were treated with CRT followed by a PDR IGBT boost from January 2009 to December 2009 in our institution. All patients had at least a partial response after CRT before IGBT. The institutional review board approved the study. Patients received a 45-Gy external beam radiotherapy (EBRT) to the pelvis with concomitant weekly cisplatin (40 mg/m) for 5 cycles. All patients then underwent reimaging using MRI before BT. The IGBT boost was accomplished with one insertion using an MRI-compatible tandem and ovoid applicator delivering 30 to 35 Gy to a high-risk clinical target volume. Treatment-induced adverse events (AEs), dose parameters, local control, progression-free survival, and overall survival are reported. RESULTS: Forty patients were included in this study, with ages ranging from 31 to 65 years (median age, 45 y). Of all the patients, 12.5% and 5% experienced grade 3 to 4 acute gastrointestinal and genitourinary AEs, respectively, and 2.5% and 2.5% had grade 3 to 4 chronic gastrointestinal and genitourinary AEs, respectively. Within a median follow-up of 30 months (range, 7 to 40 mo), local control was 90%, progression-free survival was 87.5%, and overall survival was 100%. CONCLUSIONS: Intracavitary MRI PDR-IGBT boost after CRT is a feasible, tolerable, and effective treatment modality for patients with stages IB2 and II cervical cancer.