Metastatic cervical cancer: clinical experience with pembrolizumab application. Case report

Cervical cancer (CC) ranks fourth for cancer incidences in women after breast cancer, colorectal cancer and lung cancer. There is a steady increase in the incidence of invasive forms of CC in Russia. Over the past quarter of a century, the mortality rate of reproductive age group women with cervical cancer has increased by 2 times. The standard treatment options for cervical cancer progression were the regime of paclitaxel plus cisplatin (carboplatin). The addition of an antiangiogenic therapy (bevacizumab) to the standard chemotherapy regimen increases overall survival of only 4%. The response to other lines of chemotherapy does not exceed 10% after the therapy using the combination of paclitaxel + carboplatin + bevacizumab. The results of KEYNOTE-158 trial demonstrated objective responses in 91% of CC patients lasting for more than 6 months in case of application of pembrolizumab 200 mg every 3 weeks in cases of PD-L1 expression (CPS1) with acceptable toxicity. The presented clinical case of successful treatment using pembrolizumab in women with PD-L1 expression in metastatic CC has a beneficial effect on further accumulation of experience and could help to choose the right treatment options in order to increase the efficacy of the therapy and to increase the survival rates for this category of patients.

ESMO 2020 update: Pancreatic cancer

SummaryAt the ESMO (European Society for Medical Oncology) 2020 several interesting albeit not practice-changing studies in the field of pancreatic cancer were presented. The Canadian phase II randomized PA.7 trial investigated the additional benefit of dual checkpoint inhibition with durvalumab and tremelimumab to a standard chemotherapy regimen as first-line treatment in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Unfortunately, no significant improvement of responses or outcome could be achieved rendering this study a negative trial. Within the German platform-based QoliXane trial, quality of life was shown to be an essential prognosticator of survival with fatigue and nausea being independently associated with outcome of patients. Moreover, promising results could be observed with new targeted therapy approaches, which may lead to its investigation in larger randomized clinical trials.

Characterizing the Anticancer Treatment Trajectory and Pattern in Patients Receiving Chemotherapy for Cancer Using Harmonized Observational Databases: Retrospective Study (Preprint)

BACKGROUND Accurate and rapid clinical decisions based on real-world evidence are essential for patients with cancer. However, the complexity of chemotherapy regimens for cancer impedes retrospective research on observational health databases. OBJECTIVE To compare the anticancer treatment trajectories and patterns of clinical events according to regimen type using the chemotherapy episodes determined by the algorithm. METHODS We developed an algorithm to extract the regimen-level abstracted chemotherapy episodes from medication records in a conventional Observational Medical Outcomes Partnership (OMOP) common data model (CDM) database. The algorithm was validated on the Ajou University School Of Medicine (AUSOM) database by manual review of clinical notes. Using the algorithm, we extracted episodes of chemotherapy from patients in the EHR database and the claims database. We also developed an application software that visualizing the chemotherapy treatment patterns based on the treatment episodes in the OMOP-CDM database. Using this software, we generated the trends in type of the regimen used in the institutions, the patterns of the iterative chemotherapy use, and the trajectories of cancer treatment in two of EHR based OMOP-CDM database. The time of onset of chemotherapy-induced neutropenia according to regimen was measured as a pilot study using the AUSOM database. The anti-cancer treatment trajectories for patients with COVID-19 were also visualized based on the nationwide claims database. RESULTS We generated 178,360 treatment episodes for patients with colorectal, breast, and lung cancer for 85 different regimens. The algorithm precisely identified the type of chemotherapy regimen in 300 patients (positive predictive value: 100%). The trends in the use of routine clinical chemotherapy regimen from 2008 to 2018 were identified for 8,236 patients. In a total of 12 regimens, the number of repeated treatments, which held the largest proportion of patients, was concordant with the protocols for certain cases in wiki for standard chemotherapy regimen. Moreover, the anticancer treatment trajectories for 8,315 patients were shown, including 62 patients with COVID-19. A comparative analysis of neutropenia showed that its onset in colorectal cancer regimens tended to cluster in days 9 to 15, whereas it tended to be clustered in days 2 to 8 for certain regimens for breast cancer or lung cancer. CONCLUSIONS We propose a method for generating chemotherapy episodes for introduction into the oncology extension module of the OMOP-CDM databases. The proof-of-concept studies demonstrated the usability, scalability, and interoperability of the proposed framework through a distributed research network.

HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand

Context.— Endometrial serous carcinoma is an aggressive subtype of endometrial cancer with the highest rate of recurrence and mortality among all histotypes. A recent clinical trial showed prolonged progression-free survival in advanced-stage and recurrent human epidermal growth factor receptor 2 (HER2)–positive endometrial serous carcinoma when trastuzumab was added to the standard chemotherapy regimen. This targeted therapeutic approach was recently endorsed by the National Comprehensive Cancer Network clinical guidelines. There is a growing interest among clinicians to obtain HER2 testing in endometrial serous carcinoma, and pathologists need to be prepared to recognize the unique characteristics of HER2 protein expression and gene amplification in these tumors and apply specific HER2 scoring criteria. Objective.— To provide a historical overview of targeted HER2 therapy in endometrial serous carcinoma and to summarize key findings from recent studies on the specific features of HER2 protein expression and gene amplification relative to other tumor types. Endometrial carcinoma–specific HER2 testing criteria are proposed based on evidence in the existing literature. Data Sources.— Sources comprise review of the literature and personal experience of the author. Conclusions.— HER2 protein overexpression and/or gene amplification is present in approximately 25% to 30% of endometrial serous carcinomas, providing an opportunity for targeted therapy. Pathologists play a key role in tumor HER2 testing and scoring to ensure appropriate patient selection and successful clinical outcome.

Recent Advances and Challenges in the Treatment of Rhabdomyosarcoma

Rhabdomyosarcoma, the most common soft tissue sarcoma noted in childhood, requires multimodality treatment, including chemotherapy, surgical resection, and/or radiation therapy. The majority of the patients with localized rhabdomyosarcoma can be cured; however, the long-term outcomes in patients with metastatic rhabdomyosarcoma remain poor. The standard chemotherapy regimen for patients with rhabdomyosarcoma is the combination of vincristine, actinomycin, and cyclophosphamide/ifosfamide. In recent clinical trials, modifications of the standard chemotherapy protocol have shown improvements in the outcomes in patients with rhabdomyosarcoma. In various type of malignancies, new treatments, such as molecular targeted drugs and immunotherapies, have shown superior clinical outcomes compared to those of standard treatments. Therefore, it is necessary to assess the benefits of these treatments in patients with rhabdomyosarcoma. Moreover, recent basic and clinical studies on rhabdomyosarcoma have reported promising therapeutic targets and novel therapeutic approaches. This article reviews the recent challenges and advances in the management of rhabdomyosarcoma.

Long Progression-free-survival Pancreatic Carcinosarcoma Under Gemcitabine-nabpaclitaxel First Line Chemotherapy

Carcinosarcoma of the pancreas is a rare entity with short case series reported in the literature. Diagnosis is established by immunohistochemical examination including both carcinomatous and sarcomatous components. Prognosis is usually limited to 6-9 months life expectancy. Standard chemotherapy regimen is not well defined. We present a case of pancreatic carcinosarcoma with long-time progression-free-survival under first line chemotherapy treatment with gemcitabine-nabpaclitaxel combination. Tumor histopathological and clinical characteristics are reviewed.

A clinical comparison between dedifferentiated low-grade osteosarcoma and conventional osteosarcoma

Aims The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology. Patients and Methods We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features. Results The five-year overall survival (OAS) rates in the DLOS and COS patients were 85.7% and 77.1% (p = 0.728), respectively, and the five-year progression-free survival (PFS) rates were 57.7% and 44.9% (p = 0.368), respectively. A total of 12 DLOS patients received chemotherapy largely according to regimens for COS. Among the nine cases with a histological evaluation after chemotherapy, eight showed a poor response, and seven of these had a necrosis rate of < 50%. One DLOS patient developed local recurrence and five developed distant metastases. Conclusion Based on our study of 13 DLOS cases that were strictly defined by histological and molecular means, DLOS showed a poorer response to a standard chemotherapy regimen than COS, while the clinical outcomes were not markedly different. Cite this article: Bone Joint J 2019;101-B:745–752.

Phase II trial of S-1 plus cisplatin combined with bevacizumab for advanced non-squamous non-small cell lung cancer (TCOG LC-1202)

Background S-1 plus cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC). The addition of bevacizumab has been shown to significantly improve overall survival (OS) in patients with advanced non-squamous (NSq) NSCLC who received carboplatin plus paclitaxel, however, failed to show an OS advantage in patients who received cisplatin plus gemcitabine. Methods Chemotherapy-naive patients with Stage IIIB, IV or recurrent non-SQ NSCLC were treated with a 3-week cycle of S-1 80 mg/m2 on days 1–14, cisplatin 60 mg/m2 on day 8 and bevacizumab 15 mg/kg on day 8 for 4–6 cycles. Patients without progressive disease (PD) received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 80 mg/m2 every other day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), OS, toxicity profile and Quality of life (QOL). Results From June 2013 to January 2015, 39 eligible patients were enrolled from eight institutions. Thirty-one patients (79%) completed four cycles of induction chemotherapy, and maintenance chemotherapy was initiated in 23 patients (59%). Median PFS, OS and ORR were 7.3 months (95% CI: 5.9–8.7), 21.4 months (95% CI: 14.7—not reached) and 64%, respectively. The most common grade 3/4 toxicities were leukopenia (12.8%), neutropenia (23.0%) and hypertension (28.2%). QOL analyses showed detrimental effects after initiation of the regimen. Conclusions S-1 plus cisplatin in combination with bevacizumab met the primary endpoint in patients with advanced NSq-NSCLC. RR was anticipated to be high with acceptable toxicities.

Successful Treatment with Taxane-Based Chemotherapy in Advanced Sebaceous Carcinoma: A Case Report and Literature Review

For sebaceous carcinoma (SC), a rare malignant tumor, no standard chemotherapy regimen for patients with distant metastasis has been studied. We experienced a case of eyelid SC with multiple lung metastases that responded to combination chemotherapy with carboplatin and paclitaxel with 11-month progression-free survival (PFS). This patient also responded to second-line treatment with docetaxel, another taxane, with 7-month PFS, resulting in at least 18 months of survival at the time of reporting. This report shows that taxane-based chemotherapy may be effective for advanced SC, for which no standard therapy has been established.