ABSTRACT
Neoadjuvant chemotherapy is a well-established concept in muscle-invasive bladder cancer with known advantages in overall survival. Phase II trials show encouraging response rates for neoadjuvant immunotherapy before radical surgery in urothelial cancer. There is no recommendation for neoadjuvant therapy in upper tract urothelial carcinoma before nephroureterectomy. Our aim was to assess the available data on neoadjuvant chemotherapy and immunotherapy before nephroureterectomy in patients with high-risk upper tract urothelial carcinoma in terms of pathological downstaging and oncological outcomes. Two investigators screened PubMed/Medline for comparative trials in the English language. We identified 368 studies and included eleven investigations in a systematic review and meta-analysis for neoadjuvant chemotherapy and control groups. There were no comparative trials investigating immunotherapy in this setting. All 11 studies reported on overall pathological downstaging with a significant effect in favor of neoadjuvant chemotherapy (OR 5.17; 95%CI 3.82; 7.00). Pathological complete response and non-muscle invasive disease were significantly higher in patients receiving neoadjuvant chemotherapy (OR 12.07; 95%CI 4.16; 35.03 and OR 1.62; 95%CI 1.05; 2.49). Overall survival and progression-free survival data analysis showed a slight benefit for neoadjuvant chemotherapy. Our results show that neoadjuvant chemotherapy is effective in downstaging in upper urinary tract urothelial carcinoma. The selection of patients and chemotherapy regimens are unclear.
ABSTRACT
BACKGROUND: According to previous reports, in patients with preoperative coronavirus disease 2019 (COVID-19) infection, mortality is increased if they undergo surgery within 6 weeks of diagnosis. However, the optimal timing and preoperative examination for gastrectomy with a previous COVID-19 infection are still controversial. We experienced three cases in which patients successfully underwent open radical gastrectomy following preoperative chemotherapy even though they developed COVID-19 infection during the chemotherapy. CASE PRESENTATION: Case 1: A 58-year-old man with locally advanced gastric cancer caught COVID-19 during preoperative chemotherapy comprising 5-fluorouracil, calcium folate, oxaliplatin, and docetaxel. Although the patient had specific lung shadows indicating COVID-19 infection and deep venous thrombosis in the lower extremities, he underwent distal gastrectomy 10 weeks after the COVID-19 diagnosis. He had a good postoperative course. Case 2: A 56-year-old man with gastric cancer and lymph node and peritoneal metastasis caught COVID-19 during palliative chemotherapy comprising S-1, oxaliplatin, and trastuzumab. He underwent total gastrectomy as conversion surgery 8 weeks after COVID-19 infection. His postoperative course was uneventful. Case 3: A 55-year-old man with gastric cancer and paraaortic lymph node and liver metastases caught COVID-19 during S-1 and oxaliplatin treatment as neoadjuvant chemotherapy. He underwent distal gastrectomy, paraaortic lymph node sampling, and partial hepatectomy 8 weeks after COVID-19 infection although he had residual lung shadows and deep venous thrombosis in the lower extremities. He had an uneventful postoperative course. CONCLUSIONS: Computed tomography for preoperative evaluation was performed for all three patients and revealed that lung shadows remained post-COVID-19 infection. Despite this finding, the patients had good operative courses and were discharged as planned. Surgery after 7 weeks from the diagnosis of COVID-19 infection can be performed safely even when patients are post-chemotherapy and have residual lung findings and deep venous thrombosis. This report may contribute to the development of a consensus on performing safe gastrectomy for advanced gastric cancer in patients previously infected with COVID-19.
ABSTRACT
Background: The COVID-19 pandemic imposed great burden on the healthcare system and has required patients and their physicians to make unprecedented choices about cancer care. Hospital-based retrospective reviews have suggested changes in breast cancer management during 2020 compared to previous years, including greater use of preoperative therapy. We used insurance claims data to understand the impact of the pandemic on breast cancer diagnosis and treatment at a national level. Methods: We identified new diagnoses of breast cancer from 2017-2020 in the Optum Clinformatics claims data set, consisting of claims records linked to electronic health records. The overall population (enrolled in Optum for at least 6 months with at least one diagnosis of any condition and no prior breast cancer diagnosis) included an average of 8 million adult Americans per year. A new breast cancer diagnosis was defined as a first-ever ICD code for breast cancer with a breast diagnostic biopsy procedure code (considered the cancer diagnosis date) within 6 months before to 3 months after that ICD code. Each year's cohort of breast cancer cases was limited to those diagnosed between February 1 and May 30, with follow-up through June 30 of the diagnosis year. First treatment after diagnosis was classified as either endocrine therapy, chemotherapy, or surgery. Geographic area was defined by the 9 Census Bureau regions. We used a Poisson regression to compare the rate of breast cancer diagnosis in 2020 compared to 2017-2019 and a Chi-squared test to compare the distribution of first treatment in 2020 compared to 2017-2019. To investigate differences in the impact of the pandemic on rate of diagnosis (Poissonregression) or use of preoperative therapy (logistic regression) by race/ethnicity, income, or geographic area, we included each of these covariates as well as its interaction with year (2020 vs 2017-2019) in separate models. Results: There were 2, 841 breast cancer diagnoses February-May 2020 (0.037% of overall population), compared to 3, 880 in 2019 (0.045%), 3, 509 in 2018 (0.043%), and 2, 999 in 2017 (0.041%). In 2020 compared to 2017-2019, new breast cancer diagnoses decreased by 12.3% (95% CI 8.6%-15.9%;p < 0.0001). No significant differences were observed in this reduction in diagnoses by race/ethnicity, income level, or geographic area. Median date of diagnosis was earlier in 2020 (March 11) compared to 2017-2019 (March 29, April 1, and April 1 respectively), a result of a larger drop in diagnoses later in the time interval in 2020. Among patients who received treatment during follow-up (83.1% in 2017-2019 vs 86.2% in 2020, a difference likely reflecting this shift in diagnosis date), there was a marked reduction in surgery as first treatment in 2020 compared to previous years (88.7% in 2017-2019 vs 69.3% in 2020), while both preoperative chemotherapy (6.1% in 2017-2019 vs 10.7% in 2020) and preoperative endocrine therapy (5.2% in 2017-2019 vs 20.1% in 2020) increased (p < 0.0001). There were no differences in the shift toward preoperative therapy by race/ethnicity or income, but there was a significant difference by geographic area (p=0.0003): the Mountain region had least change in use of preoperative therapy (odds ratio 2.46 [95% CI 1.75-3.47] of preoperative therapy during vs before the pandmic) while the Middle Atlantic region had the greatest (odds ratio 5.64 [95% CI 3.79-8.38]). Conclusions: Among insured U.S. patients, new breast cancer diagnoses decreased by 12.3% during February-May 2020 compared to the same period in the previous three years, and use of preoperative therapy, largely endocrine, increased by 2.7-fold. The impact of the pandemic on choice of first treatment differed by geographic area, but not by race/ethnicity or income in this insured population. We will monitor with continued follow-up of claims data to assess the longer-term impact of these pandemic-related changes on treatment patterns, cost, and patient outcomes.
ABSTRACT
The increasing use of pre-operative systemic therapy has resulted in more limited information about axillary lymph node status, both from the impact of systemic therapy itself as well as from less extensive axillary surgery. Decisions about the use of adjuvant endocrine therapy have not been majorly affected, but information on the presence and number of involved lymph nodes can have a significant influence on the use of adjuvant chemotherapy and HER-2 targeted therapies. In addition, lymph node information can also impact decisions around radiation therapy, making multidisciplinary discussions highly relevant when planning therapy. Patients with hormone receptor positive breast cancer may be treated with pre-operative endocrine therapy. This strategy was often used in early stage breast cancer during the COVID pandemic due to delays in surgery. Although an effective approach, pre-operative endocrine therapy may impact nodal status at surgery, information which is important when deciding on the use of OncotypeDX testing in premenopausal women. Similarly, in postmenopausal women, the presence and number of lymph nodes involved is a critical factor in determining the appropriateness of OncotypeDx testing. This nodal information may be lost in the setting of pre-operative therapy and would alter decisions regarding adjuvant chemotherapy. For patients with HER2 positive breast cancer, the presence of nodal disease remains critical for adjuvant decision making. In the situation of small (up to 3 cm) node negative cancers, up front surgery is preferred, because pathologic confirmation of the tumor size and node negative status may make patients eligible for a de-escalated approach of adjuvant paclitaxel and trastuzumab. Patients with more advanced HER2 positive disease are good candidates for preoperative chemotherapy and HER2 targeted therapy. If they have residual disease at surgery, they can be offered trastuzumab emtansine, which was shown in the KATHERINE trial to improve outcomes. In both situations, accurate information about the presence of disease in the axillary lymph nodes determines the most effective treatment approach. Finally, accurate information about nodal status is also relevant to decisions in patients with triple negative breast cancer. Patients who are treated with pre-operative chemotherapy and have residual disease in either the breast or axillary lymph nodes may be offered adjuvant capecitabine, based on the CREATE-X study, which indicated improved survival outcomes in those patients with residual disease who received adjuvant capecitabine. As in HER2 positive breast cancer, the presence of residual disease (including in the lymph nodes) after preoperative therapy will influence the adjuvant therapy recommendation. Thus, when considering de-escalation approaches in axillary management, the impact on systemic therapy decision making must be carefully considered, as these additional adjuvant therapies may improve survival for patients. Conflict of Interest: No significant relationships.