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.
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.
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.
Abstract Background: The impact of obesity on the survival of patients with epithelial gynecological tumors is not yet clear. We aim to elucidate the impact of body mass index (BMI) on epithelial gynecological tumors in a large tertiary center at Saudi Arabia. Methods: We retrospectively reviewed the medical files of all patients with pathologically confirmed epithelial gynecological tumors at our center. Then, we assessed the difference in overall survival (OS) according to primary tumor location, BMI, stage at presentation, and performance status (PS) at presentation using log-rank tests. Results: 400 patients were included in the analysis. The mean age at diagnosis was 56.1±13 years. 242 (60.5%) patients were diagnosed with uterine carcinomas, 137 (34.3%) with ovarian carcinomas, and 21 (5.3%) with cervical carcinomas. 278 (69.5%) patients were obese at presentation, 74 (18.5%) were overweight, 43 (10.8%) were within normal range, and 7 (1.8%) were underweight. The PS at presentation was 0, 1, 2, 3, and 4 in 351 (87.8%), 17 (4.3%), 10 (2.5%), 16 (4%), and 6 (1.5%) patients, respectively. Cervical cancer was associated with long OS, while ovarian cancers demonstrated poor prognosis (p=0.0159). There was no difference in OS between different BMI groups (p=0.072). Patients with stage 4 cancers had significantly shorter OS (p<0.0001). Patients with PS 4 at presentation was associated with the worst prognosis (p<0.0001). Interpretation: Shorter OS was associated with ovarian carcinomas, advanced staging, and poor PS at presentation. BMI classification had no impact on OS. Further studies are needed to confirm our findings. Citation Format: Ahmed Badran, Mahmoud Elshenawy, Waleed Fallatah, Abdullaah K. Hinkston, Saad S. Ali, Mohammed Ali Omar, Abdulaziz M. Alaklabi, Hytham M. Abdalla, Tarek Z. Arabi, Belal N. Sabbah, Hamed Alhusaini. The impact of obesity on survival in epithelial gynecological tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4976.
Abstract 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.
Cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors have been a significant breakthrough in the management of hormone receptor-positive, HER2-negative metastatic breast cancer based on the results of several large phase III randomized trials. The most common reported toxicity is myelosuppression due to disease such as leukopenia, neutropenia, and thrombocytopenia. Other toxicities associated with CDK 4/6 inhibitors include mucositis, fatigue, gastrointestinal side effects, hepatic toxicities, and QTc prolongation. Despite a good toxicity profile in pivotal studies, the increased rates of use in clinical practice may show less prevalent but lethal toxicity such as lung injury.Here, we describe a female patient with metastatic hormone receptor-positive/human epidermal growth factor 2-negative breast cancer who developed lung toxicity while on ribociclib.Lung injury is a possible side effect of CDK 4/6 inhibitors and there is an increasing need to understand the management of this side effect.
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
Low-grade serous ovarian cancer (LGSOC) is a very rare histological subtype of serous ovarian cancer, representing approximately 2% of all epithelial ovarian cancers. LGSOC has a better prognosis and a low response rate to chemotherapy in comparison to high-grade serous ovarian carcinoma (HGSOC).
Methodology
A retrospective review of the medical records of all patients with histologically proven LGSOC diagnosed and treated between January 2003 and December 2019.
Results
Twenty-three patients diagnosed with LGSOC and treated in KFSHRC were identified. The median age at diagnosis was 45.5 years (range 26–66). Median BMI was 26.1 (range 18–43). Twenty-one (91.3%) patients had de novo LGSOC; however, only two patients (8.7%) had been transformed and recurred from SBOT. The median BMI was 26.1 (18–46). Eight patients (34.7%) had FIGO stage IV at diagnosis, but 3 (13%),3 (13%), and 9(39%) had stages I, II, and III, respectively. Ten patients (43.8%), 5 (21.7%), and 3 (13%) had complete response (CR), stable disease (SD), and partial response (PR) after first-line therapy, respectively. At a median follow-up of 34 months (95% confidence interval (CI): 25.32–42.69), the median PFS was 75.2 months (95% CI: 17.35–133.05), and the median OS was not reached.
Conclusion
LGSOC has better PFS and OS as compared to high-grade ovarian cancer. There is systemic treatment (chemotherapy or hormonal therapy). Optimal cytoreduction is associated with better PFS and OS than suboptimal debulking. The optimal systemic chemotherapy or hormonal treatment is still controversial.
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