Combining Sunitinib and Bevacizumab for the Management of Advanced Renal Cell Carcinoma: A Phase I/II Trial.

BACKGROUND: Tyrosine kinase inhibitors remain a cornerstone in managing metastatic clear cell renal cell carcinoma (RCC). The 4 weeks on/2 weeks off intermittent sunitinib schedule could result in rebound angiogenesis and tumor progression in the 2-week rest period. We propose using bevacizumab during this period for continuous antiangiogenic effects. METHOD: This was a phase I/II study of patients with advanced clear cell RCC. Sunitinib was given 50 mg daily on a 4-week on/2-week off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. The bevacizumab starting dose was 5 mg/kg, and the dose was escalated to 10 mg if there was no dose-limiting toxicity. The primary endpoints were response rate and progression-free survival (PFS). RESULTS: Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose-limiting toxicity was observed with 5 mg bevacizumab. One patient achieved a complete response, and 12 achieved a partial response (52% response rate). At a median follow-up of 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median PFS duration was 16.5 months (95% CI 4.1-28.8), and the median overall survival time was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity; the most common were thrombocytopenia (32%), lymphopenia (32%), hypertension (28%), and fatigue (24%). CONCLUSION: Continuous angiogenesis blockade by adding bevacizumab to the sunitinib on/off regimen for advanced RCC yields significant antitumor activity with manageable increased toxicity.

Combined Prophylactic Hyperthermic Intraperitoneal Chemotherapy and Intraoperative Radiotherapy for Localized Gastroesophageal Junction and Gastric Cancer: A Comparative Nonrandomized Study.

BACKGROUND: The peritoneum frequently is the only recurrence site after radical resection of gastric cancer. Data suggest that hyperthermic intraperitoneal chemotherapy (HIPEC) and intraoperative radiotherapy (IORT) reduce peritoneal recurrence and possibly improve survival for patients with resected gastric and serosal involvement. This study aimed to evaluate the efficacy of combining prophylactic HIPEC and IORT after radical resection of localized gastric cancer. METHODS: In this retrospective study, the medical records of adult patients with histologically proven gastric/gastroesophageal adenocarcinoma who underwent radical resection with curative intent were evaluated for recurrence and survival according to whether they received prophylactic HIPEC and IORT. RESULTS: The eligibility criteria were met by 58 patients, 33 of whom underwent prophylactic HIPEC and IORT after radical surgery. Overall, 91% the HIPEC/IORT group and 72% of the surgery-only group had ≤pT3 disease. The median follow-up period was 26.6 months for the HIPEC/IORT group and 50.6 months for the surgery group. Locoregional recurrence occurred for six patients (18.1%) in the HIPEC/IORT group and five patients (20%) in the surgery-only group, with peritoneal metastasis (PM) occurring in respectively three (9%) and six (24%) patients. The median recurrence-free survival (RFS) duration was 23.2 months (95% confidence interval [CI] 6.5-39.9 months) for the HIPEC/IORT group versus 24.8 months (95% CI 0.0-51.1 months) for the surgery-only group (p = 0.88), and the corresponding 5-year overall survival (OS) estimates were 69% and 58%. CONCLUSION: Prophylactic HIPEC and IORT after radical surgery for localized gastric or gastroesophageal cancer did not improve RFS or OS for an unselected group of patients at risk for peritoneal recurrence.

Incidence and risk factors for secondary graft failure in uniformly treated patients with severe aplastic anemia receiving fludarabine and cyclophosphamide for conditioning and matched sibling bone marrow graft as stem cell source.

BACKGROUND AIMS: Graft failure after allogeneic transplant for aplastic anemia is problematic. The risk of graft failure depends on multiple variables, including the preparative regimen, donor type, stem cell dose and source among other variables. METHODS: We performed a retrospective analysis of patients with aplastic anemia who underwent matched-sibling allogeneic transplant at a single center. RESULTS: We identified 82 patients who fit the inclusion criteria. One had primary graft failure and was excluded from this analysis. The recipient median age was 22 years. The donor median age was 23 years. The median time from diagnosis to transplant was 1.6 months. The median number of red cell transfusions before transplant was nine. The median number of platelet transfusions before transplant was 18. Thirteen patients developed secondary graft failure, with a cumulative incidence at 5 years of 16% and median time to develop secondary graft failure of 129 days. All patients engrafted with a median time for neutrophil engraftment of 19 days and a median time for platelet engraftment of 22 days. The survival of patients with or without secondary graft failure was not different. Major or bidirectional ABO incompatibility and older recipient age were statistically significantly associated with greater risk of secondary graft failure. CONCLUSIONS: Secondary graft failure is a significant complication after allogeneic transplant for SAA. Identification of recipients at risk and mitigating the potential risks of this complication is warranted.

Characteristics and treatment results of patients with gastroenteropancreatic neuroendocrine tumors in a tertiary care centre.

BACKGROUND: Gastroenteropancreatic Neuroendocrine tumors (GEP-NET) are rare neoplasms with limited reported data from the Middle East. Our study aims to report the clinicopathological feature, treatment patterns, and survival outcomes of patients with GEP-NET from our part of the world. METHODS: Medical records of patients diagnosed with GEP-NET between January 2011 and December 2016 at a single center in Saudi Arabia were reviewed retrospectively, and complete clinicopathological and treatment data were collected. Patients' survival was estimated by the Kaplan-Meier method. RESULTS: A total of 72 patients were identified with a median age of 51 years (range 27-82) and male-to-female ratio of (1.1). The most common tumor location was the pancreas (29.1%), followed by small bowel (25%), stomach (12.5%), rectum (8.3%), colon (8.3%), and appendix (6.9%). Forty-one patients (57%) had well-differentiated grade (G)1, 21 (29%) had G2, and 4 (6%) had G3. In five patients, the pathology was neuroendocrine carcinoma and in one it could not be classified. 54.2% of the patients were metastatic at diagnosis. Forty-two patients underwent surgical resection as primary management while 26 underwent systemic therapy, three patients were put on active surveillance, and one was treated endoscopically with polypectomy. The 5-year overall survival and progression-free survivals were 77.2% and 49%, respectively, for the whole group. Patients with G1 and 2 disease, lower Ki-67 index, and surgically treated as primary management had significantly better survival outcomes. CONCLUSION: Our study suggests that the most common tumor locations are similar to western reported data. However, there seems to be a higher incidence of metastatic disease at presentation than in the rest of the world.

High AUF1 level in stromal fibroblasts promotes carcinogenesis and chemoresistance and predicts unfavorable prognosis among locally advanced breast cancer patients.

BACKGROUND: Locally advanced breast cancer (LABC), the most aggressive form of the disease, is a serious threat for women's health worldwide. The AU-rich RNA-binding factor 1 (AUF1) promotes the formation of chemo-resistant breast cancer stem cells. Thereby, we investigated the power of AUF1 expression, in both cancer cells and their stromal fibroblasts, as predictive biomarker for LABC patients' clinical outcome following neoadjuvant treatment. METHODS: We have used immunohistochemistry to assess the level of AUF1 on formalin-fixed paraffin-embedded tissues. Immunoblotting was utilized to show the effect of AUF1 ectopic expression in breast stromal fibroblasts on the expression of various genes both in vitro and in orthotopic tumor xenografts. Cytotoxicity was evaluated using the WST1 assay, while a label-free real-time setting using the xCELLigence RTCA technology was utilized to assess the proliferative, migratory and invasive abilities of cells. RESULTS: We have shown that high AUF1 immunostaining (≥ 10%) in both cancer cells and their adjacent cancer-associated fibroblasts (CAFs) was significantly associated with higher tumor grade. Kaplan-Meier univariate analysis revealed a strong correlation between high AUF1 level in CAFs and poor patient's survival. This correlation was highly significant in patients with triple negative breast cancer, who showed poor disease-free survival (DFS) and overall survival (OS). High expression of AUF1 in CAFs was also associated with poor OS of ER+/Her2- patients. Similarly, AUF1-positive malignant cells tended to be associated with shorter DFS and OS of ER+/Her2+ patients. Interestingly, neoadjuvant therapy downregulated AUF1 to a level lower than 10% in malignant cells in a significant number of patients, which improved both DFS and OS. In addition, ectopic expression of AUF1 in breast fibroblasts activated these cells and enhanced their capacity to promote, in an IL-6-dependent manner, the epithelial-to-mesenchymal transition and stemness processes. Furthermore, these AUF1-expressing cells enhanced the chemoresistance of breast cancer cells and their growth in orthotopic tumor xenografts. CONCLUSIONS: The present findings show that the CAF-activating factor AUF1 has prognostic/predictive value for breast cancer patients and could represent a great therapeutic target in order to improve the precision of cancer treatment.

Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women.

PURPOSE: BRCA gene mutations (BRCAm) have an impact on patients' characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women. METHODS: This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). RESULT: Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation. CONCLUSION: The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended. TRIAL REGISTRATION: Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.

Frontline-matched sibling donor transplant of aplastic anemia patients using primed versus steady-state bone marrow grafts.

Priming donors with G-CSF before BM harvest is reported to improve engraftment and GvHD in recipients. These effects are highly desirable when transplanting patients with non-neoplastic hematologic diseases, particularly AA patients. Here we retrospectively report the outcomes of 39 AA patients receiving a primed BM graft from MSD to 43 patients receiving a steady-state BM graft from MSD, otherwise transplanted using a uniform transplant platform. The graft had higher TNC and CD34 cell concentrations in the primed group (p < 0.001), and that was reflected in higher TNC and CD34 doses per kilogram of recipient in the primed group (p = 0.004 and 0.03, respectively). The OS for primed BM graft recipients was 97.4% and 78.9% for the steady-state BM graft recipients, p-value = 0.01. The cumulative incidence of death without GF was 2.6% in the primed group and 16.3% in the steady-state group, p-value = 0.03. There was no difference in GvHD incidence between the two groups. We confirm that priming improved the TNC and CD34 graft concentration and cell dose; this evidence along with other reported studies constitute reasonable evidence to prove that BM priming improve engraftment. We observed no increase in GvHD using primed BM graft.

Nodular lymphocyte-predominant Hodgkin lymphoma characteristics, management of primary and relapsed/refractory disease and outcome analysis: the first comprehensive report from the Middle East.

BACKGROUND: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon variant of Hodgkin lymphoma. There is limited data on treatment, management of refractory and relapsed disease, and long-term outcome. Many registries or country-wide data reports are unable to provide detailed primary and subsequent management. We are reporting our observation on patient's characteristics, management, and outcome. METHODS: This single-institution retrospective cohort analysis includes NLPHL patients seen from 1998 to July 2019. We used Fisher's exact test, chi-square, and Kaplan-Meier (KM) method for various analyses. RESULTS: Two hundred patients were identified, (6.34% of all the HL). Male:female was 3:1. The median age at diagnosis was 22 years (4-79 years). Stage I-II in 145 (72.5%) cases. One hundred patients (50%) received chemotherapy, 68 (34%) chemotherapy + radiation therapy (RT); 87% of all chemotherapy was ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). Thirteen patients (6.5%) received RT alone and 16 (8%) had surgery alone. Complete response in 82%, partial response in 5.5% and progressive disease in 10.5%. The median follow is 60 months (5-246). Median 5 and 10 years overall survival (OS) is 94.8 and 92.4% (stages I-II, 97.7 and 97.7%, stage III-IV, 94.8 and 92.4%). Median event-free survival (EFS) is 62.3 and 54% respectively (stage I-II, 72 and 64%, stage III-IV, 36.4 and 18.2%). Stage I-II vs III-IV OS (p = < 0.001) and EFS (p = < 0.001) were significant. For stage I-II, 5 year EFS of chemotherapy + RT (83.3%) was superior to chemotherapy alone (60%, p = 0.008). Five year EFS for early favorable (80%), early unfavorable (60%), and advanced (36.4%) was significant (p = < 0.001). Eleven patients (5.5%) had high-grade transformation. Twenty-nine patients underwent HDC auto-SCT, all are alive (28 in remission). 25% of patients had pathologically proved nodal hyperplasia at some point in time. CONCLUSION: OS of NLPHL is excellent and independent of treatment type. EFS is better for chemotherapy + RT than chemotherapy alone. Stem cell transplant in refractory / multiple relapses resulted in excellent disease control. There is a need to identify optimal treatment strategies accordingly to the risk stratification.

Does the Timing of Surgery after Neoadjuvant Therapy in Breast Cancer Patients Affect the Outcome?

BACKGROUND: There is a paucity of literature examining the impact of timing of surgery after neoadjuvant chemotherapy. OBJECTIVE: This study aimed to analyze the impact of the time taken to initiate surgical treatment following completion of neoadjuvant chemotherapy on patients' outcomes by evaluating their pathological response, overall survival (OS), and disease-free survival (DFS). METHODS: This is a retrospective review of 611 patients diagnosed with stage II and III breast cancer that received neoadjuvant chemotherapy and surgery between January 2004 and December 2014. The data was collected from a prospectively gathered registry. The patients were stratified into three cohorts according to the time of surgery after neoadjuvant chemotherapy: <4 weeks, 4-7 weeks, or ≥8 weeks. Outcomes were assessed using Kaplan-Meier curves, and the variables were compared using log-rank statistics. RESULTS: The 5-year OS rate was 89.6% and the 5-year DFS rate was 74%. OS and DFS were not significantly different when stratified according to timing of surgery; however, the trends of OS and DFS were poor when surgery was delayed for ≥8 weeks. Median OS and median DFS have not yet been reached. Of the 17% of patients that had surgery after ≥8 weeks, 12.9% had pathological complete response (pCR), while among those that received surgery 4-7 weeks and <4 weeks after neoadjuvant chemotherapy, 26% and 21% had pCR, respectively (p = 0.02). ER+/HER-2+ patients had a statistically significant decrease in pCR if surgery was performed after ≥8 weeks. CONCLUSION: Our patients showed improved pCR if surgery was performed within 8 weeks, especially for ER+/HER-2+ patients. All patients had better OS and DFS trends if surgery was performed between 4 and 7 weeks after neoadjuvant chemotherapy.

CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma.

BACKGROUND: Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined. METHODS: Retrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared. RESULTS: There was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR = 8.5, p = < 0.001) and overall survival (OS, HR = 13, p = 0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR = 4.0, p = 0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p = 0.008) and low CD3+ TIL (p = 0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n = 58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR = 7.2, p = < 0.001) and OS (HR = 17.3, p = 0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR = 6.1, p = 0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p < 0.001). CONCLUSIONS: CD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3 + TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials.

Comparison of closed system transfer devices for turnaround time and ease of use.

OBJECTIVE/PURPOSE: The primary purpose of this study was to compare three closed-system transfer devices with differing mechanical interfaces for their suitability for adoption into our daily practice. The secondary purpose was to use the results of this study to support the selection of one of the closed-system transfer devices, which would suit both the pharmacy and nursing staff at our institution, furthermore promoting the enculturation of international recommendations into our clinical practice. STUDY DESIGN/METHODS: The hazardous drug preparation process was observed and timed continuously from the moment the technician started compounding until the finished product was handed to the designated checker by raising hands. A self-administered, structured questionnaire was used for data collection looking at ease of use of each of the devices from the perspective of pharmacy technicians and nurses. The questionnaire contained an open-ended 10-point Likert-type scale of eight domains. RESULTS/KEY FINDINGS: An improvement in the compounding efficiency of hazardous drugs using PhaSeal™ ( n = 46), ChemoLock™ ( n = 45), and EquaShield® II ( n = 45), when compared respectively against the historical control ( n = 86), was statistically significant ( p < 0.001). However, no statistically significant difference among the different closed-system transfer devices for preparation of hazardous drugs was observed in our study ( p = 0.1). In terms of ease of use, there was no difference in preference for ChemoLock™ and Equashield®II among the pharmacy technicians with both scoring a mean score of 10 with regard to implementation. While PhaSeal™ scored a mean score of 7.2. Among the nursing staff there was a slight preference for ChemoLock™ over Equashield®II with a mean score of 9.2 and 9, respectively with regard to the recommended product, while PhaSeal™ scored a mean score of 7.4. Both nursing staff and pharmacy technicians had a preference ChemoLock™, with a mean score of 10 and 9.6, respectively in terms of on how easy was each device/system to use and overall impression for pharmacy technicians. This was followed by Equashield®II with a mean score of 9.8 and 8.6, respectively and then PhaSeal™ with a mean score of 7.2 and 6.6, respectively. Pharmacy technicians felt there were more steps, packaging and clutter when using PhaSeal® in comparison to the other devices. With Equashield® II, the estimation of clutter was higher than that of ChemoLock™ despite the number of packages being within a similar range. CONCLUSION/RECOMMENDATIONS: Our study found that with experienced staff, compounding of hazardous drugs with closed-system transfer devices can be as efficient as or even more so than with the traditional needle and syringe method. With the lack of statistically significant difference among the different closed-system transfer devices studied, in addition to the cost, ease of use was one of the factors that decided the products applicability in our institution.

Survival analysis of patients with Hodgkin lymphoma who failed high dose chemotherapy and autologous stem cell transplant.

Hodgkin lymphoma (HL) patients failing after high dose chemotherapy (HDC) and auto-SCT have a poor outcome. Some patients may still benefit from further treatments. From 1996 to 2016, 137 HL patients (39.5%) out of 347 transplanted experienced post auto-SCT failure. Males/female 61%:39%, median age at auto-SCT 23.4 years and median follow-up 55.6 months (9-153). Type of failure was progressive (46%), relapsed (35%) or persistent disease/refractory disease (19%). Median overall survival (OS) from the time of failure is 20 months; 35 patients (25.5%) are alive. One hundred and four patients received treatment; the response rate was 45%; complete remission in 41 (30%) and partial remission in 21 (15%) patients. 1st interventions post auto-SCT were chemotherapy (39%), radiation therapy (35%) or best supportive care (24%). Twenty-seven patients with 2nd-SCT (allogeneic (15), auto-SCT (2)) and/or brentuximab (18 patients) had superior OS (50.6 months) vs other treatments (22.5 months, P value 0.037). COX regression multivariate analysis identified post auto-SCT treatment failure before 12 months (hazard ratio (HR) 3.37, CI 1.7-6.6, P value < 0.001), presence of B symptoms (HR 2.55, CI 1.4-4.6, P value 0.002), stages III-IV (HR 2.7, CI 1.5-4.9, P value 0.001), albumin < 4 g/dl (HR 1.76, CI 1.1-2.9, P value 0.027) and tumor > 5 cm (HR 1.1.9, CI 1.13-3.25, P value 0.015) as significant risk factors; P value < 0.001. KM OS with 0-1 factor (148.6 months): 2 factors (23.6 months) and 3-5 factors (9.4 months) (P value < 0.001). OS was 63%:25%:7% respectively with 0-1:2:3-5 factors respectively (P value < 0.001). Despite high-risk factors, 2nd-SCT/brentuximab use post HDC auto-SCT failure may result in durable survival.

Translation and validation of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) version 4 quality of life instrument into Arabic language.

BACKGROUND: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) has been translated from English into several languages. Currently, there is no validated translation of FACT-BMT in Arabic. Here, we are reporting the first Arabic translation and validation of the FACT-BMT. METHODS: The study was approved by the Institutional Research Advisory Council. The Arabic translation followed the standard Functional Assessment of Chronic Illness Therapy (FACIT.org) translation methodology (with permission). Arabic FACT-BMT (50- items) was statistically validated. Cronbach's alpha for internal consistency, Spearman's rank correlation coefficients method for Inter-scale correlations and Principal Component Analysis for factorial construct validity was used. RESULTS: One hundred and eight consecutive relapsed /refractory lymphoma patients who underwent high dose chemotherapy and autologous stem cell transplant were enrolled. There were 68 males (63%) and 40 females (37%) with a median age of 29 years (range 14-62). After Arabic questionnaire pre-testing (Cronbach's alpha 0.744), the study included 108 patients. Cronbach's alpha for the entire FACT-BMT indicated an excellent internal consistency (0.90); range (0.67 to 0.91). Cronbach's alpha for sub-groups of social (0.78), emotional (0.67) and functional wellbeing was (0.88). Cronbach's alpha for bone marrow transplant (0.81), FACT-General (0.89), and FACT- Trial Outcome Index (TOI); (0.91) also revealed excellent internal consistency. Patients had high scores in all domains of quality of life, indicating that most patients were leading a normal life. This translation of FACT-BMT in Arabic was reviewed and approved for submission by the FACIT.org. CONCLUSIONS: Our data reports the first translated, validated and approved Arabic version of FACT-BMT. This will help large numbers of Arabic speaking patients undergoing stem cell/bone marrow transplantation, across the globe.

Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma.

High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin's lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14-21 years) and young adult (>21-30 years) (AYA) HL patients. We used Fine and Gray's competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS-death, the multivariate analysis identified complete remission (CR) duration of <12 months (hazard ratio (HR) 3.61, P = 0.0009), no CR after salvage (HR: 3.93, P = 0.0002), and nodular sclerosis pathology (HR 3.3, P = 0.016) and positive B symptoms (HR 2, P = 0.028) as negative factors. For DS-event, CR duration of <12 months (HR 1.88, P = 0.02), no CR after salvage (HR 3.47, P = 0.000005) and nodular sclerosis pathology (HR 1.88, P = 0.02) were found significant. The Kaplan-Meier method estimated overall survival (OS) at 36 months with 0-2:3:4 factors being 93.6:54:21 %, respectively (P value <0.001). Kaplan-Meier estimated event-free survival (EFS) at 36 months with 0-1:2:3 factors being 84.6:65:31 %, respectively (P value <0.001). Clinically, adolescents have similar outcomes as young adults.

Phase II Trial of FOLFIRINOX in Advanced Biliary Tract Cancer.

INTRODUCTION: Biliary tract cancers (BTCs), characterized by poor prognosis and limited treatment options, are increasingly prevalent malignancies with a five-year survival rate of less than 20% for advanced-stage disease. The standard first-line chemotherapy combining gemcitabine and cisplatin offers modest survival benefits, necessitating the exploration of more effective therapies. This study reports the results of a single-arm, open-label, phase 2 trial assessing the efficacy and safety of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) as a first-line treatment for metastatic or locally advanced unresectable BTC. METHODS: Patients aged ≥18 with measurable disease and adequate organ function were enrolled, receiving biweekly FOLFIRINOX for up to 12 cycles with follow-up imaging every four cycles. The primary endpoint was the overall response rate (ORR), with progression-free survival (PFS), overall survival (OS), and safety as secondary endpoints. RESULTS: Thirteen patients were enrolled from December 2016 to September 2021 before early termination due to slow accrual and the emergence of immunotherapy. The ORR was 54%, with a disease control rate of 77%. Median PFS and OS were 6.8 and 19.25 months, respectively. Grade 3/4 toxicities were predominantly hematologic, with neutropenia being the most common severe adverse event. CONCLUSION: The trial suggests that FOLFIRINOX is a potentially effective first-line therapy for unresectable or metastatic BTC with a manageable safety profile. However, the early termination of the study and the introduction of immunotherapy warrant further research to confirm these findings.

Outcome and prognostic factors of low­grade serous ovarian cancer: An observational retrospective study.

Low-grade serous ovarian cancer (LGSOC) is a very rare histological subtype of serous ovarian cancer, representing ~2% of all epithelial ovarian cancer cases. LGSOC has a better prognosis but a lower response rate to chemotherapy in comparison to high-grade serous ovarian carcinoma (HGSOC). The present study is a retrospective review of the medical records of all patients with histologically proven LGSOC diagnosed and treated in a single institute between January 2003 and December 2019. A total of 23 patients diagnosed with LGSOC and treated at King Faisal Specialist Hospital and Research Center (Riyadh, Saudi Arabia) were identified. The median age at diagnosis was 45.5 years (range, 26-66 years) and the median body mass index was 26.1 (range, 18-43). A total of 21 patients (91.3%) had de novo LGSOC, whereas only 2 patients (8.7%) had LGSOC that had transformed from serous borderline ovarian tumors and recurred. A total of 8 patients (34.8%) were diagnosed with International Federation of Gynecology and Obstetrics stage IV, whereas 3 (13.0%), 3 (13.0%) and 9 (39.1%) were diagnosed with stages I, II and III, respectively. In addition, 10 (43.5%), 5 (21.7%), and 3 (13.0%) patients had complete response, stable disease and partial response statuses after first-line therapy, respectively. At a median follow-up time of 34 months [95% confidence interval (CI), 25.32-42.69], the median progression-free survival (PFS) time was 75.2 months (95% CI, 17.35-133.05) and the median overall survival (OS) time was not reached. In conclusion, LGSOC exhibited better PFS and OS times than HGSOC as compared with data from the literature, and there is the option for systemic treatment (chemotherapy or hormonal therapy). Optimal cytoreduction showed numerically higher, but non-significant, PFS and OS times compared with suboptimal debulking; however, the optimal systemic chemotherapy or hormonal treatment remains controversial.

The Effectiveness of Denosumab in Middle Eastern Patients With Giant Cell Tumor of the Bone: A Single-Center, Retrospective Study.

BACKGROUND: Giant cell tumor of the bone (GCTB) is an aggressive benign tumor, which constitutes 5% of all primary bone tumors. Denosumab, a receptor activator of nuclear factor κB ligand monoclonal antibody, inhibits osteoclast-induced bone destruction and has demonstrated promising results in patients with GCTB. However, the long-term efficacy of the drug has not been extensively studied, especially in the Middle East. METHODOLOGY: In this study, we retrospectively analyzed the five-year progression-free survival (PFS) in patients with GCTB at a single Saudi center. PFS was defined as the time from diagnosis until disease progression, relapse, or death. Events were censored after five years from diagnosis. RESULTS: Sixty-two patients with GCTB were included in the study. The median age at diagnosis was 31.16 years, and 38 (61.3%) patients were female. Twenty-nine patients (46.8%) received denosumab during the study period. The median duration of denosumab treatment was 5.06 months, and the median number of cycles was 6. The median PFS was not reached, and the five-year PFS rate was 60.3%. Age, gender, body mass index, performance status at presentation, and tumor location had no impact on five-year PFS. Denosumab treatment prolonged PFS; however, this was not statistically significant compared to non-denosumab patients (P = 0.603). CONCLUSIONS: Denosumab does not seem to provide superior long-term outcomes compared to surgery alone. Although our findings are generally consistent with other studies in the literature, larger long-term studies are needed to confirm our findings.

Outcomes of Autologous stem cell transplantation in patients with primary refractory Diffuse Large B-cell lymphoma who demonstrate chemosensitivity to salvage chemotherapy.

Rituximab with anthracycline-based combination frontline chemoimmunotherapy can cure 50-60% of patients with diffuse large B-cell lymphoma (DLBCL). However, studies on the outcomes of patients with DLBCL who experience partial response (PR), stable or progressive disease in response to frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) therapy are limited, as are data on the outcomes of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in patients with primary refractory DLBCL who demonstrate chemosensitivity to salvage chemotherapy (SC). We assessed the latter among 184 patients, 144 of whom started SC, with 84 responding and 72 receiving HDC-ASCT. The 5-year survival rate was 58.9%; the median overall survival (OS) was not reached. The difference in response to SC (partial response versus complete response) was significant, with higher 2- and 5-year OS rates in patients with CR (78.1% and 74.9%, respectively) than in those with PR (55.3% and 47%, respectively). The median OS for the whole group was 15 months and particularly patients who had progressive disease after frontline R-CHOP had dismal outcomes. Our study suggests that in patients with primary refractory DLBCL without initial progressive disease after frontline R-CHOP, the depth of response to SC before HDC-ASCT is predictive of relapse.

Efficacy of Chemotherapy Rechallenge Versus Regorafenib or Trifluridine/Tipiracil in Third-Line Setting of Metastatic Colorectal Cancer: A Multicenter Retrospective Comparative Study.

PURPOSE: Metastatic colorectal cancer (mCRC) is a significant global health burden. This retrospective study compared the effectiveness of trifluridine/tipiracil (FTD/TPI), regorafenib, and chemotherapy rechallenge for third-line mCRC treatment. MATERIALS AND METHODS: We reviewed the medical records of 132 patients with mCRC treated with regorafenib, FTD/TPI, or a rechallenge with the initial chemotherapy regimen in a third-line setting from four different institutions. The primary end point was progression-free survival (PFS). Secondary end points were objective response rate and overall survival (OS) across the three treatment approaches. RESULTS: Twenty-nine patients received chemotherapy rechallenge, and 103 received FTD/TPI or regorafenib. Patients' characteristics were comparable, except for a lower number of left-sided primaries and KRAS wild-type tumors in the FTD/TPI-regorafenib group. The median PFS for the entire group was 3.0 months, and the median OS was 13.7 months. Chemotherapy rechallenge has resulted in a median PFS of 3.1 months and a median OS of 21.2 months, compared with 2.9 months (PFS) and 12.6 months (OS) for the FTD/TPI-regorafenib group. Multivariate analyses identified male sex and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 as independent prognostic factors for better PFS, whereas chemotherapy rechallenge, localized stage at diagnosis, and an ECOG PS of 0-1 were significant prognostic factors for better OS. CONCLUSION: This study suggests that chemotherapy rechallenge may provide a survival benefit in the third-line treatment of mCRC. However, patient characteristics, such as sex and ECOG PS, should also be considered in treatment decisions. Further prospective studies are required to confirm our findings.