Treatment patterns after poly-ADP ribose polymerase (PARP) inhibitors in epithelial ovarian cancer patients.

OBJECTIVES: The primary objective of this study was to describe treatment patterns after poly-ADP ribose polymerase (PARP) inhibitor in patients with epithelial ovarian cancer. Secondary objectives were to evaluate duration of response, time to first subsequent therapy, progression-free survival and overall survival. METHODS: This was a retrospective analysis of patients with epithelial ovarian cancer treated with PARP inhibitor therapy at six Australian gynecological oncology centers. Eligible patients were identified via clinics, trial databases and pharmacy dispensing logs between January 2005 and September 2019. Information regarding clinico-pathological characteristics and treatment outcomes were collated from medical records. RESULTS: A total of 85 patients with epithelial ovarian cancer were identified. Of these, 61% had germline BRCA1/2 mutations, 9% had somatic BRCA1/2 mutations, 5% had confirmed homologous recombination deficiency and 25% were BRCA1/2 wildtype mutations. A total of seventy-seven (91%) patients received chemotherapy after PARP inhibitor, with fifty-six (72.7%) of these patients receiving platinum-based chemotherapy. Four patients (5%) had a complete response, 15 (20%) a partial response, 15 (20%) stable disease and 41 (55%) progressive disease. Median duration of response to chemotherapy was 7.0 months (range 0.2-20.4). Median time to first subsequent therapy was 17.6 and 15.1 months in patients who received a PARP inhibitor as maintenance therapy and treatment, respectively. Median progression-free survival of first line treatment after PARP inhibitor was 9.6, 3.5 and 4.6 months for platinum doublet, single agent platinum and non-platinum chemotherapy, respectively. Adjusting for age and FIGO (Federation of Gynecological Oncologists classification) stage progression-free survival did not differ between treatment groups (p=0.14). Median overall survival for the cohort was 69 months, and patients with platinum sensitive ovarian cancer had improved survival compared with those with platinum refractory or resistant disease. CONCLUSION: Platinum doublet chemotherapy resulted in non-significant improved progression-free survival compared with other regimens, suggesting potential independent mechanisms of resistance between PARP inhibitor and platinum compounds.

Interobserver and intraobserver variability of RECIST assessment in ovarian cancer.

OBJECTIVES: Measurement of Response Evaluation Criteria In Solid Tumors (RECIST) relies on reproducible unidimensional tumor measurements. This study assessed intraobserver and interobserver variability of target lesion selection and measurement, according to RECIST version 1.1 in patients with ovarian cancer. METHODS: Eight international radiologists independently viewed 47 images demonstrating malignant lesions in patients with ovarian cancer and selected and measured lesions according to RECIST V.1.1 criteria. Thirteen images were viewed twice. Interobserver variability of selection and measurement were calculated for all images. Intraobserver variability of selection and measurement were calculated for images viewed twice. Lesions were classified according to their anatomical site as pulmonary, hepatic, pelvic mass, peritoneal, lymph nodal, or other. Lesion selection variability was assessed by calculating the reproducibility rate. Lesion measurement variability was assessed with the intra-class correlation coefficient. RESULTS: From 47 images, 82 distinct lesions were identified. For lesion selection, the interobserver and intraobserver reproducibility rates were high, at 0.91 and 0.93, respectively. Interobserver selection reproducibility was highest (reproducibility rate 1) for pelvic mass and other lesions. Intraobserver selection reproducibility was highest (reproducibility rate 1) for pelvic mass, hepatic, nodal, and other lesions. Selection reproducibility was lowest for peritoneal lesions (interobserver reproducibility rate 0.76 and intraobserver reproducibility rate 0.69). For lesion measurement, the overall interobserver and intraobserver intraclass correlation coefficients showed very good concordance of 0.84 and 0.94, respectively. Interobserver intraclass correlation coefficient showed very good concordance for hepatic, pulmonary, peritoneal, and other lesions, and ranged from 0.84 to 0.97, but only moderate concordance for lymph node lesions (0.58). Intraobserver intraclass correlation coefficient showed very good concordance for all lesions, ranging from 0.82 to 0.99. In total, 85% of total measurement variability resulted from interobserver measurement difference. CONCLUSIONS: Our study showed that while selection and measurement concordance were high, there was significant interobserver and intraobserver variability. Most resulted from interobserver variability. Compared with other lesions, peritoneal lesions had the lowest selection reproducibility, and lymph node lesions had the lowest measurement concordance. These factors need consideration to improve response assessment, especially as progression free survival remains the most common endpoint in phase III trials.

Immunotherapy associated pain crisis and the haemophagocytic lymphohistiocytosis syndrome in advanced melanoma: Case report and review of the literature.

BACKGROUND: Immunotherapy is increasingly used in the management of early and advanced malignancy. There is limited data regarding the associations between immunotherapy, malignancy, pain and haemophagocytic lymphohistiocytosis. CASE: A 40-year-old woman was diagnosed with advanced melanoma, with metastases to her brain, liver, lung, adrenal glands and bone. She had moderate opioid requirements prior to the initiation of therapy. Following doublet immunotherapy with nivolumab and ipilimumab, she experienced a severe pain crisis associated with pyrexia and haemophagocytic lymphohistiocytosis. POSSIBLE COURSES OF ACTION: Management dilemmas included whether or not to initiate non-steroidal and steroidal anti-inflammatory therapies, how to address the patient's nociceptive, neuropathic and inflammatory pain, and how to manage the haemophagocytic lymphohistiocytosis. FORMULATION OF MANAGEMENT PLAN: The patient required rapid up-titration of analgesia, including methadone, ketamine, hydromorphone, pregabalin and benzodiazepines. Ketorolac and high dose steroid therapy were administered for pain management and to mitigate treatment associated inflammation and haemophagocytic lymphohistiocytosis. OUTCOME: The patient's pain was inadequately managed despite multimodal analgesia, and stigmata of inflammation progressed. She died 14 days following treatment. LESSONS: The case demonstrates that severe pain may be a consequence of immunotherapy given for advanced, high volume melanoma. RESEARCH AVENUES: There is laboratory evidence suggesting an association between immunotherapy, malignancy, pain and haemophagocytic lymphohistiocytosis. Further clinical evidence is required in order to understand these intersecting phenomena.

The impact of ageism in the care of older adults with cancer.

PURPOSE OF REVIEW: This review summarizes recent research on the impact of ageism in older adults with cancer and how society can best address the issue. Despite older individuals representing the vast majority of those with cancer, with a dramatic increase in incidence anticipated in the coming decades, ageism remains an under-recognized and extremely detrimental phenomenon in cancer care. RECENT FINDINGS: We examine the associations between ageism and health, and highlight the consequences of higher mortality, a deterioration in mental and physical health, worse functional status and increased comorbidity burden. We then discuss the oncologic-specific impacts of ageism, including lower rates of cancer screening, decreased histological confirmation of cancer, decreased surgical intervention and systemic therapy prescription and poorer survivorship experience. To conclude, we illustrate the opportunities within oncologic systems of care to engage with, and dismantle, the damaging effects of ageism, namely policy and legislation, education and intergenerational contact. SUMMARY: Despite recognition of the numerous negative sequelae of ageism, there remains a paucity of literature regarding the intersection between ageism and cancer. Our piece summarizes the key developments in this field, but further evaluation is desperately required.

Destructive soft tissue metastases in advanced colorectal cancer: a case report.

Extremity soft tissue metastases are a rare, but recognised complication of advanced colon cancer. There is limited data regarding their management, and such metastases are associated with a poor prognosis. The investigation of such metastases may require full-body positron emission tomography (PET) scanning, rather than per-protocol PET scanning. We present the case of a 76-year-old incarcerated male with a history of T4b N1b M0 right colon adenocarcinoma, who presented with right distal thigh pain and gross disfigurement. MRI demonstrated an erosive, verrucous soft tissue lesion, which had not been present on the diagnostic, per-protocol PET scan. Whole-body PET scan subsequently confirmed a highly avid lesion, with biopsy confirming metastatic adenocarcinoma consistent with colonic origin. The patient's pain was treated with multimodal analgesia and radiotherapy. Despite these interventions, locoregional symptoms from the extremity metastasis were difficult to control. The patient died 4 months following the diagnosis of metastatic disease. This case highlights the importance of recognising extremity soft tissue abnormalities as a possible consequence of advanced colon cancer. It illustrates the importance of whole-body PET scanning and explores management complexities that may present when caring for incarcerated patients. The subsequent literature review explores the existing literature regarding extremity soft tissue metastases in colon cancer. Further data regarding both the incidence and optimal management of such lesions is required.