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Chances, risks and limitations of neoadjuvant therapy in surgical oncology.

ABSTRACT: Over the last decades, neoadjuvant treatment has been established as a standard of care for a variety of tumor types in visceral oncology. Neoadjuvant treatment is recommended in locally advanced esophageal and gastric cancer as well as in rectal cancer. In borderline resectable pancreatic cancer, neoadjuvant therapy is an emerging treatment concept, whereas in resectable colorectal liver metastases, neoadjuvant treatment is often used, although the evidence for improvement of survival outcomes is rather weak. What makes neoadjuvant treatment attractive from a surgical oncology viewpoint is its ability to shrink tumors to a smaller size and to increase the chances for complete resection with clear surgical margins, which is a prerequisite for cure. Studies suggest that local tumor control is increased in some visceral tumor types, especially with neoadjuvant chemoradiotherapy. In some other studies, a better control of systemic disease has contributed to significantly improved survival rates. Additionally, delaying surgery offers the chance to bring the patient into a better general condition for major surgery, but it also confers the risk of progression. Although it is a relatively rare event, cancers may progress locally during neoadjuvant treatment or distant metastases may occur, jeopardizing a curative surgical treatment approach. Although this is seen as risk of neoadjuvant treatment, it can also be seen as a chance to select only those patients for surgery who have a better control of systemic disease. Some studies showed increased perioperative morbidity in patients who underwent neoadjuvant treatment, which is another potential disadvantage. Optimal multidisciplinary teamwork is key to controlling that risk. Meanwhile, the neoadjuvant treatment period is also used as a "window of opportunity" for studying the activity of novel drugs and for investigating predictive and prognostic biomarkers of chemoradiotherapy and radiochemotherapy. Although the benefits of neoadjuvant treatment have been clearly established, the risk of overtreatment of cancers with an unfavorable prognosis remains an issue. All indications for neoadjuvant treatment are based on clinical staging. Even if staging is done meticulously, making use of all recommended diagnostic modalities, the risk of overstaging and understaging remains considerable and may lead to false indications for neoadjuvant treatment. Finally, despite all developments and emerging concepts in medical oncology, many cancers remain resistant to the currently available drugs and radiation. This may in part be due to specific molecular resistance mechanisms that are marginally understood thus far. Neoadjuvant treatment has been one of the major advances in multidisciplinary oncology in the last decades, requiring a dedicated treatment team and an optimal infrastructure for complex oncology care. This article discusses the goals and novel directions as well as limitations in neoadjuvant treatment of visceral cancers.

SUBMITTER: Lordick F

PROVIDER: S-EPMC6753981 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNeoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer.MethodsBased on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010-2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0).ResultsOf 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson-Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET.ConclusionsAlthough the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing.

Project description:The COVID-19 pandemic has dramatically affected everyone's daily life in one way or another, requiring a re-negotiation of existing strategies for work-life integration, not only for individuals but also within families and partnerships. To contribute to existing knowledge on work-life integration during COVID-19 in Germany, we look at gender and parenthood differences in the experiences of work-to-family (WFC) and family-to-work (FWC) conflicts. By accounting for employees' previous conflict experiences, we were able to reveal the extent to which the current conditions contributed to differences in these conflicts. Moreover, we explored the relevance of demands and resources in the family and work spheres as a way to explain different levels of WFC and FWC across gender and parenthood. Our analyses are based on a sample of 660 employees from a German linked employer-employee panel study and a COVID-19 follow-up survey conducted in late 2020. Results revealed that work-family conflict experiences before the pandemic play an important role in current conflict perceptions. Whereas WFC were more likely to be accentuated during the pandemic, prior FWC experiences may have helped to mitigate conflicts under these new conditions. Work-family conflicts in general have increased during the COVID-19 pandemic, but this finding applied only to conflicts in the family-to-work direction. Although such increases were not limited to parents, they were particularly high in this group. Overall, gender differences in work-family conflicts were absent, but differences were found between mothers and fathers. The need to compensate for a lack of external childcare, as well as having to work from home, increased FWC, especially among fathers. This study suggests that FWC in particular became more important during the pandemic; however, parents were not the only ones who were disadvantaged when it came to work-life integration; childless individuals likewise struggled to balance the demands of work and private life.

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Chances, risks and limitations of neoadjuvant therapy in surgical oncology.

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