Christopher E. Desch
Christopher E. Desch
Neelima Denduluri, Debra A. Patt, Yunfei Wang, Menaka Bhor, Xiaoyan Li, Anne M. Favret, Phuong Khanh Morrow, Richard L. Barron, Lina Asmar, Shanmugapriya Saravanan, Yanli Li, Jacob Garcia, and Gary H. Lyman
Background: A wide variety of myelosuppressive chemotherapy regimens are used for the treatment of cancer in clinical practice. Neutropenic complications, such as febrile neutropenia, are among the most common side effects of chemotherapy, and they often necessitate delays or reductions in doses of myelosuppressive agents. Reduced relative dose intensity (RDI) may lead to poorer disease-free and overall survival. Methods: Using the McKesson Specialty Health/US Oncology iKnowMed electronic health record database, we retrospectively identified the first course of adjuvant or neoadjuvant chemotherapy received by patients without metastases who initiated treatment between January 1, 2007, and March 31, 2011. For each regimen, we estimated the incidences of dose delays (≥7 days in any cycle of the course), dose reductions (≥ 15% in any cycle of the course), and reduced RDI (<85% over the course) relative to the corresponding standard tumor regimens described in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Results: This study included 16,233 patients with 6 different tumor types who received 1 of 20 chemotherapy regimens. Chemotherapy dose delays, dose reductions, and reduced RDI were common among patients treated in community oncology practices in the United States, but RDI was highly variable across patients, regimens, and tumor types (0.486–0.935 for standard tumor regimen cohorts). Reduced RDI was more common in older patients, obese patients, and patients whose daily activities were restricted. Conclusions: In this large evaluation of RDI in US clinical practice, physicians frequently administered myelosuppressive agents at dose intensities lower than those of standard regimens.
Vanderbilt-Ingram Cancer Center
Occult primary tumors, or cancers of unknown primary, account for 5% to 10% of all diagnosed cancers, and are manifested by a wide variety of clinical presentations, while conferring a poor prognosis for most patients. Even after postmortem examination, the primary tumor is not identified in 20% to 50% of patients. Multiple sites of involvement are observed in more than 50% of patients. Although certain patterns of metastases suggest possible primaries, occult primaries can metastasize to any site. In most patients, occult primary tumors are refractory to systemic treatments, and chemotherapy is only palliative and does not significantly improve long-term survival. However, special pathologic studies can identify subsets of patients with tumor types that are more responsive. Treatment options should be individualized for this selected group to achieve improved response and survival rates. Important updates for the NCCN guidelines include the additions of tables on tumor-specific markers and their staining pattern as well as analysis of undifferentiated carcinoma.
For the most recent version of the guidelines, please visit NCCN.org
Meaghan Tenney and Joan L. Walker
Minimum surgical treatment for endometrial cancer is removal of the uterus. The operative approach to achieve that goal ranges from vaginal hysterectomy alone to laparotomy with radical hysterectomy, bilateral salpingoophorectomy, bilateral pelvic and para-aortic lymphadenectomy with possible omentectomy, and resection of all metastatic disease. Stratifying the risk factors for predicting presence of metastatic disease has error rates exceeding tolerance for many gynecologic oncologists. Most accept routine laparoscopic surgical staging with hysterectomy, pelvic and para-aortic lymphadenectomy, and removal of adnexa as standard care for patients with endometrial cancer. Modifying the extent of surgical staging for low-risk intrauterine findings or excessive risk for postoperative morbidity is also accepted. Laparoscopic surgery has become the ideal initial surgical approach for this disease, allowing for visual inspection of common metastatic sites, biopsy of abnormal areas, and cytology from peritoneal surfaces. The extent of staging can be altered depending on frozen section findings from the uterus, adnexa, and peritoneal surfaces. Intraoperative medical decision-making can be individualized, encompassing all known risk factors for metastases and balancing comorbidities and potential adverse outcomes. This article documents how laparoscopic surgery satisfies the needs of individual patients and surgeons treating this disease.
Katy K. Tsai, Neharika Khurana, Timothy McCalmont, Adil Daud, Boris Bastian, and Iwei Yeh
Clear cell basal cell carcinoma (BCC) is an unusual variant of BCC. Its pathogenesis, prognosis, and optimal management remain poorly described due to its rarity. This report presents a 51-year-old man with a history of excised BCC and cutaneous squamous cell carcinomas of the face, with multiple recurrent poorly differentiated carcinomas with clear cell changes of the shoulder for which further classification using conventional histologic means was not possible. His tumor tissue was sent to Foundation Medicine for testing, which revealed a high number of pathogenic genomic alterations, including a mutation in PTCH1. He was diagnosed with dedifferentiated BCC and started on vismodegib. He developed lung metastases while receiving vismodegib, and his disease continued to progress while he was undergoing treatment in a phase I clinical trial. Given the high number of pathogenic alterations suggestive of high tumor mutational burden, immunotherapy was considered and off-label authorization was obtained for treatment with a PD-1 antibody (pembrolizumab). He had a dramatic disease response after 4 infusions of pembrolizumab. Molecular testing was instrumental in determining the correct diagnosis and formulating appropriate treatment options for this patient. Molecular profiling of metastatic BCCs and its subtypes is essential to the development of effective targeted therapies and combination approaches.
Alan N. Houghton
Priyanka Reddy, James Martin, and Alberto Montero
the entire cohort were 21.5 months and 57.6 months, respectively. 84.1% of patients with bone-only disease were alive at 60 months compared to 41.8% in patients with mixed bony and visceral metastases (p=0.004). Similarly, patients with bone
Yao Zhu, Yu Wei, Hao Zeng, Yonghong Li, Chi-Fai Ng, Fangjian Zhou, Caiyun He, Guangxi Sun, Yuchao Ni, Peter K.F. Chiu, Jeremy Y.C. Teoh, Beihe Wang, Jian Pan, Fangning Wan, Bo Dai, Xiaojian Qin, Guowen Lin, Hualei Gan, Junlong Wu, and Dingwei Ye
Background: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. Patients and Methods: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. Results: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1–11.1), BRCA2 (OR, 15.3; 95% CI, 10.0–23.2), MSH2 (OR, 15.8; 95% CI, 4.2–59.6), and PALB2 (OR, 5.9; 95% CI, 2.7–13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34–3.58] and 2.47 [95% CI, 1.23–4.96], respectively) but similar benefit from docetaxel. Conclusions: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.
Sharon M. Weinstein, Dorothy Romanus, Eva M. Lepisto, Cielito Reyes-Gibby, Charles Cleeland, Rex Greene, Cameron Muir, and Joyce Niland
The National Comprehensive Cancer Network (NCCN), an organization of 19 of the world's leading cancer centers, developed and communicated a cancer pain treatment guideline. NCCN seeks to implement guidelines through performance measurement using a NCCN Oncology Outcomes Database. This is a preliminary report from the NCCN Cancer Pain Management Database Project. The primary objective of this NCCN Cancer Pain Management Database Project study is to evaluate the frequency, methods, and extent of documentation of cancer pain assessment and managementat NCCN institutions. A pain data dictionary and related data collection forms were first developed. The records of 209 breast cancer patients with bone metastases were then studied. The frequency of pain mentions, type of pain assessment tool used, pain characteristics, type of clinician documenting pain, location in the medical record, and pain treatment characteristics were noted. The majority of clinical encounters included pain mentions, although considerable variability was found in pain documentation between providers and between inpatient and outpatient settings. Nurses more frequently recorded pain, usually as a numeric pain intensity score. Pain specialists were more likely to record a complete description of pain. A significant minority of patients experienced moderate to severe pain. In a small subgroup of patients with moderate to severe pain, pain treatment was not recorded. The undertreatment of cancer pain has been a focus of investigation and review for the past two decades. Quality improvement efforts to raise the standard of pain management have been underway. The results of this study highlight the need for standardization of pain documentation in comprehensive cancer centers as a prerequisite for the proper assessment of cancer pain and the improvement of clinical outcomes of pain management.