Maximizing Regulatory Review Efficiency: The Evolution of the FDA OCE RTOR Pilot

To promote the efficient review of oncology drug applications, the US Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) launched the Real-Time Oncology Review (RTOR) pilot program in 2018. RTOR allows FDA to review individual sections of eCTD modules of a drug application for oncology drugs in contrast to requiring the applicant to submit complete modules or the complete application before review is initiated. Initially, the program accepted only supplemental applications with simple study designs and easily interpretable endpoints, but the scope has since been expanded to include applications for New Molecular Entities (NME), and other applications with more complex features. Though many applicants experience faster approvals under RTOR, it is difficult to isolate the effect of the RTOR program on review timelines as its contribution is masked by other expedited programs like priority review and breakthrough therapy designation (BTD). This article discusses the expanded scope of RTOR, its interplay with other OCE initiatives to modernize regulatory review, summarizes Genentech’s experiences in planning RTOR submissions from February 2019 to July 2021, and provides considerations for the future of the program.

Infleunce of Body Mass Index (BMI) on Outcome of Colon Cancer in Relationships with Other Clinicopathological Factors

Background: Colon cancer is the third most common cancer. High (BMI) contributes hazardously for several types of malignancies including colon cancer while the effect of BMI as a prognostic factor is poorly defined. Objective: Demonstrating the influence of increasing (BMI) on colon cancer recurrence. Patients and Methods: Case-control study involved a sample of 312 patients and 131 patients were excluded from this study and only 181 patients of colon cancer are included in the study with stage 2 and 3 who did underwent a surgical operation and received adjuvant chemotherapy recruited from an oncology teaching hospital, Al Jawad oncology center (Alkadhemiya hospital) and Babylon Oncology center. Results: The study involved 181 patients of colon cancer patients with mean age of 56.25 ±11.74years the highest proportion of study patients (90.6%) were aged more than 40yrs with a male to female ratio (1.2:1). Overweight patients constituted 39.2% and obese 23.8% and normal body weight 37%. In this study majority of tumors are ulcerating for about 72.5% and sigmoid and left side colon was the most common site of the tumor in about 53% with stage three is a most common type. Regarding recurrence, 54.1% of study patients have recurrence, and the majority of the 41.8% occurs between 1-3years after primary tumors diagnoses and treatment with a high prevalence of recurrence was seen in obese patients (74.4%) with a significant association between prevalence of recurrence and increasing BMI. In this study, 61.2% of patients with lymphovascular invasion have recurrences of malignancy with significant associations between recurrences and LVIe. Also more than 50% of patient older than 40years got recurrences with significant associations between recurrences with age of patients. In this study we take the effect of each clinicopathological feature on the outcome of colon cancer and then to excluded its effect by logistic regression to see the effect of only BMI on the outcome of colon cancer. Conclusion: Increase body mass index is associated with increase recurrence of colon cancer Keywords: Colon cancer recurrence, body mass index, Clinicopathological Factors

Phẫu thuật ung thư khoang miệng có tạo hình khuyết hổng bằng vạt dưới cằm

TÓM TẮT Đặt vấn đề: Ung thư khoang miệng chiếm tỷ lệ 30% ung thư đầu cổ và 2.0% trong ung thư nói chung. Phẫu thuật phải đảm bảo cắt rộng u với diện cắt an toàn để hạn chế tái phát, nhưng thường để lại khuyết hổng khá lớn. Vạt dưới cằm được sử dụng rộng rãi trong tạo hình khuyết hổng vùng khoang miệng, có đặc điểm: tỷ lệ sống cao, linh hoạt. Nghiên cứu này nhằm đánh giá hiệu quả của vạt dưới cằm trong tạo hình khuyết hổng sau cắt ung thư khoang miệng tại khoa Phẫu Thuật - Trung tâm Ung Bướu - Bệnh viện Trung Ương Huế từ tháng 4/2020 - 8/2021. Đối tượng và phương pháp nghiên cứu: Đây là nghiên cứu tiến cứu can thiệp lâm sàng không nhóm chứng trên 8 trường hợp sử dụng vạt dưới cằm trong tạo hình khuyết hổng sau cắt ung thư khoang miêng. Kết quả: Kích thước vạt trung bình là 28 cm2 (4 x 7 cm), tái tao khuyết hổng vùng lưỡi 3 trường hợp, lưỡi sàn miệng 4 trường hợp, niêm mạc má và góc hậu hàm 1 trường hợp. Bệnh nhân được ăn qua đường miệng sau 8 ngày, xuất viện sau 12 ngày. Biến chứng: Rò miệng - cổ 2 trường hợp, hoại tử 1 phần vạt: 1 trường hợp. Sau 1 tháng, các vạt lành tốt, chức năng khoang miệng ảnh hưởng ít (chức năng nhai nuốt và phát âm ảnh hưởng ít). Sau 6 tháng, ghi nhận 7/8 trường hợp không tái phát tại chỗ, các vạt lành tốt, chức năng khoang miệng bình thường, 1 trường hợp tái phát tại chỗ. Kết luận: Vạt dưới cằm có tỷ lệ sống cao hỗ trợ lấp khuyết hổng vùng khoang miệng. ABSTRACT ORAL CANCER SURGERY WITH RECONSTRUCTION DEFECTS BY SUBMENTAL FLAP Introduction: Globally, oral cancer accounts for 30% of head and neck cancers and 2.0% of all cancer. The surgery must remove the tumor with safe marginal resection to limit recurrence; however, it causes large defects. The submental flap is gaining popularity as a technique for reconstructing oral defects, with advantages: high survival rate and flexibility. This study aimsto evaluate the efficacy of the submental flap in reconstructive defects after oral cancer surgery at the Department of Oncology Surgery - Oncology Center of Hue Central Hospital from April 2020 to August 2021. Methods: A prospective study was conducted on 8 patients who had defects reconstructed by a submental flap after oral cancer surgery. Results: The average dimension of the submental flap was 28 cm2 (4 x 7 cm). The reconstructed sites included: tongue (3 cases), floor of mouth (4 cases), buccal mucosa (1 case). Patients had oral feeds after 8 days, discharged after 12 days. Complications: Oro - cutaneous fistula (2 cases), partial necrosis (1 case). After one month, the flaps were survival, and the oral cavity function had reduced (swallowing and speech function were quite limited). After six months, 7/8 cases had no locoregional recurrence; the flap was good, and the oral cavity function was normal. One case had local recurrence. Conclusions: Submental flap is a valid option for reconstructing intra - oral soft tissue with a high survival rate. Keywords: Oral cancer, submental flap.

The Use of the Nursing Interventions Classification in Identifying the Workload of a Nursing Team in a Pediatric Oncology Center

The activities/interventions performed by the nursing team and the time required for their performance have become a widely discussed topic due to their impact on the quality of patient safety and staff working conditions. Nursing Interventions Classification (NIC) was used as a more accurate indicator as it identified activities/interventions. This study analyzed the workload distribution of nursing team in a pediatric oncology center.

Normalization of the Mini-MAC (Mental Adjustment to CanCer) Questionnaire among Cancer Patients

Cancer is associated with discomfort and many changes in patients’ lives to which they must adapt. The main objective of the study was to assess the use of the mini-MAC questionnaire scale among persons diagnosed with malignant cancer and to develop standards allowing differentiation of patients with diagnosed cancer in terms of their style of adjustment to the disease. The mini-MAC questionnaire is a widely used tool in assessing coping strategies among cancer patients. Sten standards have been developed to determine the level of results on the questionnaire scales in the low–average–high categories. The study included 1187 patients diagnosed with malignant cancer who are covered by outpatient care at the Maria Sklodowska-Curie Institute—Oncology Center in Warsaw. The questionnaire concerning mental adjustment to cancer was used (mini-MAC). Patients with cancer most often adopt strategies of fighting spirit and positive reevaluation. The variables that differentiate the results most significantly include gender, presence of metastasis, and the state of undergoing chemotherapy. The mini-MAC questionnaire should be a tool for psycho-oncological diagnosis of patients’ attitudes towards cancer. The obtained results indicate that cancer patients are characterized by their constructive style of adjustment to the disease.

Molecular Characterization of Inflammatory Tumors Facilitates Initiation of Effective Therapy

Inflammatory myofibroblastic tumor (IMT) is a rare, mesenchymal tumor that has an increased incidence in childhood. Tumors are usually isolated to the chest, abdomen, and retroperitoneum, but metastatic presentations can be seen. Presenting symptoms are nonspecific and include fever, weight loss, pain, shortness of breath, and cough. Approximately 85% of IMTs harbor actionable kinase fusions. The diagnosis can be delayed because of overlapping features with inflammatory disorders, such as elevated inflammatory markers, increased immunoglobin G levels, fever, weight loss, and morphologic similarity with nonmalignant conditions. We present a girl aged 11 years with a TFG-ROS1 fusion–positive tumor of the lung that was initially diagnosed as an immunoglobin G4–related inflammatory pseudotumor. She underwent complete left-sided pneumonectomy and later recurred with widely metastatic disease. We then report the case of a boy aged 9 years with widely metastatic TFG-ROS1 fusion–positive IMT with rapid molecular diagnosis. In both children, there was an excellent response to oral targeted therapy. These cases reveal that rapid molecular testing of inflammatory tumors is not only important for diagnosis but also reveals therapeutic opportunities. Targeted inhibitors produce significant radiologic responses, enabling potentially curative treatment approaches for metastatic ROS1 fusion IMT with previously limited treatment options. Primary care pediatricians and pediatric subspecialists have a crucial role in the early consultation of a pediatric oncology center experienced in molecular diagnostics to facilitate a comprehensive evaluation for children with inflammatory tumors.