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.

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.

Risk of hematological malignancies in the families of patients treated for nodular lymphocyte-predominant Hodgkin lymphoma.

BACKGROUND: Familial clustering of lymphoid and/or hematological malignancies (FHM) provides an opportunity to study the responsible genes. The data is limited in patients with lymphoid and hematological malignancies. METHODS: The lymphoma database was used to identify patients seen in our institution from 1998 to 2019 with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We studied FHM by collecting detailed history of any malignancy in the family (FM). RESULTS: Two hundred NLPHL patients were identified. Contacting was not possible in 30 patients due to no response to the phone calls (22) and death [1]. 170/200 patients were interviewed; represented 167 families (3 patients with a family member with NLPHL). These 170 patients provided information about 8225 family members. These 167 families had a total of 329 family members with 334 malignancies (including 167 NLPHL patients and 5 members with 2 malignancies each). Of these 167 patients, 77 (46.1%) had no FM while 90 (53.9%) patients had a positive FM; 162 family members with 167 malignancies. Among these 167 families, 31 families (18.6%) had members with FHM +/- solid cancers. These 31 families had 35 family members (25 males:10 females) with 16 lymphomas: diffuse large B cell lymphoma [2], follicular center cell lymphoma [3], chronic lymphocytic leukemia/small lymphocytic lymphoma [3], non-Hodgkin lymphoma [2], classical HL [2], and NLPHL [4]. Total of 8 leukemia: acute lymphoblastic leukemia [4], acute myeloid leukemia [3], and leukemia - no subtyping [5]. These 35 FHM members are 1st [6], 2nd (16), and 3rd [7] degree relatives of 31 NLPHL patients. There are 4 families with NLPHL in family members; all these 8 NLPHL patients are male and are alive. The median total number of 1st + 2nd +3rd degree members are 81. The decrease in the age of diagnosis from 1st generation to the 2nd generation (anticipation) was noted in 13/17 patients; 2nd generation median age at diagnosis was 29.7 years vs 1st generation age 53 years (developed malignancy 23.3 years earlier). CONCLUSION: FHM is frequent in NLPHL. This study provided us many important insights for planning future studies in terms of interviewing technique, time, and resource allocation and genetic testing.

Survival benefit of surgical resection after first-line triplet chemotherapy and bevacizumab in patients with initially unresectable metastatic colorectal cancer.

BACKGROUND: Surgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here, we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC. PATIENTS AND METHODS: Patients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of capecitabine, oxaliplatin, irinotecan, and bevacizumab. Patients were given 5-8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity, or patient request. All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and 2 monthly intervals thereafter. Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy. RESULTS: Fifty-three patients were enrolled. The median age was 52 years (range 23-74), 29 (55%) were males, ECOG PS 0-1 was 13 (66%), 11 (42%) had a right-sided tumor, 29 (55%) had resection of their primary tumor, 22 (42%) had a single metastatic site, and 8 (15.1%) had a liver-limited disease. Thirteen patients (24.5%) underwent surgical resection of residual metastatic disease +/- the primary tumor with 10 (18.9%) of them were R0. The surgical group had a higher incidence of males compared to the non-surgical group (69.3% vs 47.2%, p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p = 0.09), higher mutant Kras (53.8% vs 34.2%, p = 0.3), and higher response rate (84.6% vs 56.2%, p = 0.3). With a median follow-up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI) 9.1-20] and the median OS was 28.2 months (95% CI 22.5-53.3). The median PFS for the surgery group was 18.9 months (95% CI 12.6-not reached) compared to 9.6 months (95% CI 7.0-18.3) for the non-surgical group, log-rank p = 0.0165. The median OS for both groups was not reached (95% CI 53.3-not reached) and 23.2 months (95% CI 17.0-28.4) respectively, log-rank p = 0.0006. Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively. CONCLUSIONS: Patients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01311050 , registered March 6, 2011, retrospectively registered.

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.

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.

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.

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.

Suspected NUT carcinoma progressing on pembrolizumab, carboplatin, and paclitaxel as first-line treatment: a case report.

Introduction and importance: NUT carcinoma of the thorax is an extremely rare neoplasm characterized by a translocation between the NUT M1 gene and members of the bromodomain genetic family. Due to the rarity of the neoplasm, standardized treatment guidelines have not yet been established. Several chemotherapeutic agents have been used with limited success, due to the rapid development of resistance to treatment. Pembrolizumab, an anti-programmed-death-1 antibody, has become increasingly used in non-small-cell lung carcinomas. Consequently, pembrolizumab may be beneficial in the treatment of NUT carcinoma. Case presentation: In this article, we discuss the case of a 24-year-old man who was referred to our centre due to an incidental mass finding on an unrelated computed tomography scan. Morphological and immunohistochemical characteristics are highly suspicious of NUT carcinoma with bone metastasis. The patient was placed on carboplatin, paclitaxel, and pembrolizumab as first-line therapy. The patient later progressed and began receiving second-line treatment according to Ewing's protocol. 20 months later, the mass continued to grow, and the patient was started on docetaxel and gemcitabine, which was unsuccessful. After discussing with the patient, he decided to stop chemotherapy and begin palliative care. Clinical discussion: NUT carcinoma is an aggressive tumour with poor prognosis. Treatment options are limited and pembrolizumab does not seem to influence the clinical outcome of the neoplasm. Conclusion: Overall, pembrolizumab does not seem to improve the outcomes of NUT carcinoma patients. To the authors' knowledge, this is the second article reporting the effects of pembrolizumab on the progression of NUT carcinoma.

Rare Case of Recurrent Adamantinoma of the Tibia: Limited Efficacy of Pazopanib as a Standalone Treatment.

BACKGROUND Adamantinoma is a rare low-grade malignant bone tumor, usually found in the tibial diaphysis and metaphysis, with histological similarities to mandibular ameloblastoma. The most effective treatment of recurrent adamantinoma is not yet clear. This report is of a 22-year-old woman with recurrent tibial adamantinoma treated with the tyrosine kinase inhibitor pazopanib. CASE REPORT We report the case of a 22-year-old woman who was referred to our center for a suspicious bone lesion in the right tibia. Bone biopsy findings were consistent with an adamantinoma. En bloc resection was completed successfully, with no postoperative complications. Five years later, a positive emission tomography scan revealed mildly increased tracer uptake near the area of the previous lesion and in the right inguinal lymph node. Biopsies of the lesion and inguinal lymph node confirmed recurrence of the adamantinoma. Due to abdominal and pelvic metastasis, the patient underwent surgical debulking, along with an appendectomy, right salpingo-oophorectomy, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Subsequently, the patient was placed on pazopanib for 4 months; however, her tumor continued to worsen after 4 months of chemotherapy. Currently, the patient is receiving gemcitabine and docetaxel as second-line medical therapy. CONCLUSIONS This report showed that pazopanib as standalone treatment does not appear to have promising role on patient outcomes. To the best of our knowledge, this is the second report of pazopanib in the treatment of adamantinoma.

Characteristics and outcomes of small bowel adenocarcinoma: 14 years of experience at a single tertiary hospital in Saudi Arabia.

Small bowel adenocarcinoma (SBA) is an extremely rare cancer type. In the present study, the patient characteristics and clinical outcomes of patients diagnosed and treated for SBA at a single tertiary hospital were reported. All patients diagnosed and managed between 2007 and 2020 were reviewed. Regression analysis was used to assess variables associated with the metastatic stage at diagnosis. The Kaplan-Meier method was used to estimate survival and the log-rank test was used to determine factors associated with survival outcomes. Out of 137 cases of small bowel primary tumor, 43 consecutive patients with SBA were diagnosed with a median age of 53 years and the majority (76.7%) were males. The common initial presenting symptoms were abdominal pain (58.8%) and bowel obstruction (30.2%). The most common primary site was the duodenum (60.5%) and the majority (65.1%) were diagnosed with stage III/IV disease. Patients with a high neutrophil-lymphocyte ratio (NLR) (≥0.85) were more likely to be in the metastatic stage at diagnosis (P=0.01). The 3-year overall survival (OS) rates based on stage were 100% (I), 85% (II), 53% (III) and 33.9% (IV) (P=0.001). In addition to the stage, the Eastern Cooperative Oncology Group Performance Status (P<0.001), NLR (P<0.001), hypoalbuminemia (P=0.02) and chemotherapy in a metastatic setting (P=0.02) were prognostic factors for OS. In conclusion, NLR is a potential prognostic biomarker for a metastatic stage at diagnosis. Advanced stage, lower performance status score, low albumin level and high NLR are associated with short OS.

Successful Recovery of COVID-19 Associated With Cardiomyopathy in Advanced Breast Cancer Patient With Pulmonary Lymphangitis Carcinomatosis.

SARS-CoV-2 infection induces myocardiopathy in 19% of severe cases, with a mortality rate of up to 51%. The mainstay of treatment is supportive care, steroids, and tocilizumab (anti-IL-6). This is a case of a 43-year-old woman diagnosed with hormone-positive breast cancer with lung metastasis and pulmonary lymphangitis carcinomatosis (PLC). Her baseline cardiac function was within normal limits. She presented to the emergency department with respiratory distress. Chest CT showed multiple bilateral ground-glass opacities consistent with COVID-19 pneumonia and confirmed by COVID-19-PCR nasal swab. Her condition deteriorated, and she was urgently admitted to the intensive care unit with evidence of a cytokine storm. She was started on tocilizumab, dexamethasone, and meropenem. Echocardiogram (echo) showed a severely reduced ejection fraction with severe global hypokinesis. A second dose of tocilizumab was given, and the dexamethasone dose was increased. Fortunately, the patient had significant clinical and biochemical improvement and regained her normal cardiac function. In conclusion, dexamethasone and tocilizumab could be promising aids in treating cardiomyopathy secondary to SARS-CoV-2 infection.

Gemcitabine-Induced Myositis in a Luminal B Breast Cancer patient: A Case Report.

Human epidermal growth factor receptor-positive breast cancer is an aggressive cancer which represents approximately a quarter of all breast cancers worldwide. Recent advances have led to the development of targeted therapies, such as trastuzumab (H), which have significantly improved prognosis. Such therapies are currently used alongside other chemotherapeutic agents, such as paclitaxel (P) and gemcitabine (G). The most common side effects of PGH combination therapy include thrombocytopenia and anemias. However, there have been no previous reports of myositis resulting from this combination. We report the case of a 54-year-old metastatic breast cancer patient on PGH therapy who developed muscle weakness. The patient was initially treated with trastuzumab, pertuzumab, and paclitaxel. However, pertuzumab was changed to gemcitabine due to severe diarrhea. After the fourth cycle of PGH, the patient presented with muscle weakness and creatine kinase levels of up to 6755 U/L. Magnetic resonance imaging of the femur and pelvis revealed diffuse bilateral myositis, suggesting a diagnosis of gemcitabine-induced myositis. The patient was placed on intravenous fluids and corticosteroids, which resolved her condition. To our knowledge, this is the first report of gemcitabine-induced myositis in a breast cancer patient. Further studies are needed to determine the underlying mechanisms of gemcitabine-induced myositis and develop preventative measures.

Impact of Risk Factors and Long Term Survival Analysis of Patients With Primary Refractory Hodgkin Lymphoma Who Underwent High Dose Chemotherapy and Autologous Stem Cell Transplant.

Patients with primary refractory Hodgkin lymphoma (ref-HL) can still be salvaged with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Outcomes of patients with ref-HL is poorer than those with relapsed HL, but most studies have included patients with both relapsed and refractory diseases, and separate analyses or studies on patients with ref-HL are limited. This study aimed to evaluate the outcomes of HDC auto-SCT and impact of various prognostic factors in patients with ref-HL at the time of primary treatment failure and subsequent survival at the time of failure post-HDC auto-SCT. This retrospective single-institution cohort analysis using an HDC and auto-SCT database was approved by the Institutional Research Advisory Counsel and Ethics Committee for identifying patients. We used the Fine and Gray competing risk analysis method, a regression model for outcome analysis, and the Kaplan-Meier (KM) method for survival analysis. The study cohort comprised 200 consecutive ref-HL patients who underwent HDC auto-SCT between 1996 and 2019. The median patient age was 22.75 years, and median follow-up was 106 months. Post-auto-SCT disease status was complete remission (CR) in 122 patients (61%), partial remission in 22 (11%), and progressive disease in 47 (23.5%). KM median progression-free survival (PFS) after auto-SCT was 43.9 months (5 years, 49.3%; 10 years, 45.5%). Median overall survival (OS) was 168.6 months (5 years, 61.2%: 10 years, 56.2%). Eighty-five patients (44.5%) died, 69 (34.5%) due to disease. Multivariate analysis identified similar adverse factors for both PFS and OS. For PFS, these adverse factors included stage III-IV at relapse (hazard ratio [HR], 1.65; P = .045), mediastinal involvement (HR, 2.01; P = .009), and absence of CR after salvage chemotherapy (HR, 2.2; P = .001). PFS with 0 or 1 adverse factors (not reached), 2 adverse factors (40.8 months), and 3 adverse factors (5.4 months) was significant (P < .001). For OS, significant adverse factors included stage III-IV at relapse (HR, 1.68; P = .045), mediastinal involvement (HR, 2.52; P = .007), and no CR after salvage chemotherapy (HR, 2.15; P = .004) were significant. OS with 0 or 1 adverse factors (not reached), 2 adverse factors (148.5 months), and 3 adverse factors (34.4 months) was significant (P < .001). The median OS after auto-SCT failure was 23.6 months; patients received post auto-SCT brentuximab/second SCT (not reached), other treatments (22.5 months), and supportive care (8.4 months) (P < .001). OS with 5 risk factors present at HDC auto-SCT failure- stage III-IV, failure at <12 months, tumor >5 cm, B symptoms, and low serum albumin-was 152 months for 0 or 1 risk factors, 30.9 months with 2 risk factors, and 9.45 months with 3 to 5 risk factors (P < .001). Ref-HL patients have encouraging survival after HDC auto-SCT and can even be salvaged after auto-SCT failure. Based on prognostic factors, survival prediction is possible. Patients who fail to respond to HDC auto-SCT may benefit from newer treatments strategies and may qualify for enrollment in clinical trials.

The Use of Crizotinib in Sclerosing Epithelioid Fibrosarcoma with ALK Mutation: A Case Report.

Sclerosing epithelioid fibrosarcoma is an ultra-rare and aggressive high-grade fibrosarcoma that was originally described in 1995. More than 100 cases are documented worldwide, with the most extensive case series reporting a high rate of recurrence and metastasis. ALK mutations are commonly seen in soft-tissue sarcomas; however, this is the first known case of an ALK V757M mutation. Here, we present a case using crizotinib in treating an ALK-positive sclerosing epithelioid fibrosarcoma refractory to all traditional treatment options.

Peripheral blood eosinophil count is associated with response to chemoimmunotherapy in metastatic triple-negative breast cancer.

Introduction: There is evidence for an association between peripheral blood eosinophil count (PBEC) and response to cancer immunotherapy; however, such data is limited in metastatic triple-negative breast cancer (mTNBC). Patients & methods: This report presents patients (n = 14) who received a combination of durvalumab and paclitaxel for mTNBC (NCT02628132). Results: There was a statistically significant correlation (p = 0.028) between an increase in PBEC (>300/mm3) during treatment and response to the combination therapy. Survival analysis showed a statistically significant association between progression-free survival and increased PBEC, after therapy (p = 0.005). A similar trend existed for overall survival, although it did not reach statistical significance (p = 0.167). Conclusion: This is the first study to report on eosinophilia in mTNBC treated with chemoimmunotherapy and supports a role for eosinophils in immunotherapy for mTNBC.

Plain language summary Previous reports have shown that an increase in peripheral blood eosinophil count is associated with a good response to cancer immunotherapy; however, data on this association is limited in a subtype of breast cancer called metastatic triple-negative breast cancer (mTNBC). The eosinophil count in patients who received the combination of an immunotherapeutic agent, durvalumab and a chemotherapeutic agent, paclitaxel, in mTNBC was assessed. There was a statistically significant association between an increase in eosinophils during treatment and the response to therapy. The progression of the disease was slower or less likely to occur in patients with increased eosinophils. This study supports the role of eosinophils in immunotherapy for mTNBC.

Adult-Type Ovarian Granulosa Cell Tumour: Treatment Outcomes From a Single-Institution Experience.

OBJECTIVES:  Ovarian granulosa cell tumour is rare. This study aims to report the clinical characteristics and long-term outcomes of adult-type ovarian granulosa cell tumour (AOGCT) at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and to determine the prognostic factors affecting relapse and survival. METHODS: We retrospectively reviewed patients with AOGCT, from 1988 to 2014, who were treated at our institution. Baseline characteristics, pathological findings, and outcomes were analysed and reported. RESULTS: Sixty-one patients with AOGCT were identified with a median age of 49 years. Median follow-up was 5.0 years (range 2.1-8.2 years). 74% of patients were FIGO (International Federation of Gynecology and Obstetrics) stage I, whereas 7% were stage II, 5% were stage III, and unknown in 14% of the cases. The most common presenting symptoms included abdominal pain (43%) and vaginal bleeding (43%). The majority of patients (38 patients, 62%) were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Five (8%) patients received adjuvant chemotherapy. Sixteen patients (26%) relapsed with a median time to relapse of 5.5 years (0.7-8.1 years). Half of the recurrences (eight patients, 50%) occurred after five years of diagnosis. Five-year overall survival and disease-free survival (DFS) were 93% and 84%, respectively. Factors associated with a high risk of recurrence were the presence of ascites (p=0.000) and elevated preoperative CA 125 level (p=0.048). The overall survival was significantly influenced by the menopausal status (premenopausal 100% vs. postmenopausal 84%; p=0.02), preoperative CA 125 (normal 100% vs. elevated 64%; p=0.005), ascites (present 33% vs. absent 100%; p=0.000), and age (<55 years 100% vs. ≥ 55 years 77%; p= 0.002). CONCLUSION:  This study confirms a good outcome for patients with AOGCT. They require long-term follow-up as late recurrences can occur many years post definitive therapy. The presence of ascites and elevated preoperative CA 125 levels were associated with a higher risk of recurrence and poor prognosis. Outcomes appear unaffected by fertility-sparing surgery or adjuvant chemotherapy.

Neoadjuvant concurrent chemoradiotherapy using infusional gemcitabine in locally advanced rectal cancer: A phase II trial.

INTRODUCTION: Gemcitabine is a well-known radiosensitizer. Herein, we tested the efficacy and toxicity of preoperative concurrent infusional gemcitabine and radiotherapy in locally advanced rectal cancer. PATIENTS AND METHODS: This was a phase II, single-arm trial. Eligible patients had a diagnosis of rectal adenocarcinoma with clinical stage T3-T4 and/or nodal involvement, age ≥18 years, and no prior chemotherapy or radiotherapy. Patients received preoperative radiation at a dose of 50.4-54 Gy over 28 days with concurrent infusional gemcitabine administered at a dose of 100 mg/m2 over the course of 24 h weekly for 6 weeks. The primary endpoint was pathological complete response (pCR). RESULTS: Forty patients were recruited. Only one patient did not complete therapy due to death. Eight patients did not undergo surgery, one died, two progressed to nonresectable disease, and five withdrew consent. Five patients progressed prior to surgery, with two having unresectable metastases and three having resectable liver metastases. One was found to have peritoneal metastasis during surgery. Out of the 32 patients who underwent surgery, seven achieved pCR at a rate of 20%. With a median follow-up of 30 months, four additional patients had a distant relapse (one had a subsequent local relapse). The 3-year event-free and overall survival rates were 70% and 85%, respectively. The commonest preoperative grade 3-4 toxicity included lymphopenia (50%), neutropenia (41%), anemia (15%), diarrhea (12%), abdominal pain (12%), and proctitis (8%). CONCLUSION: Concurrent preoperative chemoradiotherapy using infusional gemcitabine for locally advanced rectal cancer achieved an encouraging degree of local control with manageable toxicity.