De-ESCAlating RadioTherapy in breast cancer patients with pathologic complete response to neoadjuvant systemic therapy: DESCARTES study.

PURPOSE: Neoadjuvant systemic therapy (NST) is increasingly used in breast cancer patients and depending on subtype, 10-89% of patients will attain pathologic complete response (pCR). In patients with pCR, risk of local recurrence (LR) after breast conserving therapy is low. Although adjuvant radiotherapy after breast conserving surgery (BCS) reduces LR further in these patients, it may not contribute to overall survival. However, radiotherapy may cause early and late toxicity. The aim of this study is to show that omission of adjuvant radiotherapy in patients with a pCR after NST will result in acceptable low LR rates and good quality of life. METHODS: The DESCARTES study is a prospective, multicenter, single arm study. Radiotherapy will be omitted in cT1-2N0 patients (all subtypes) who achieve a pCR of the breast and lymph nodes after NST followed by BCS plus sentinel node procedure. A pCR is defined as ypT0N0 (i.e. no residual tumor cells detected). Primary endpoint is the 5-year LR rate, which is expected to be 4% and deemed acceptable if less than 6%. In total, 595 patients are needed to achieve a power of 80% (one-side alpha of 0.05). Secondary outcomes include quality of life, Cancer Worry Scale, disease specific and overall survival. Projected accrual is five years. CONCLUSION: This study bridges the knowledge gap regarding LR rates when adjuvant radiotherapy is omitted in cT1-2N0 patients achieving pCR after NST. If the results are positive, radiotherapy may be safely omitted in selected breast cancer patients with a pCR after NST. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov on June 13th 2022 (NCT05416164). Protocol version 5.1 (15-03-2022).

Biopsy-Guided Pathological Response Assessment in Breast Cancer is Insufficient: Additional Pathology Findings of the MICRA Trial.

BACKGROUND: Neoadjuvant systemic treatment (NST) leads to pathologic complete response (pCR) in 10-89% of breast cancer patients depending on subtype. The added value of surgery is uncertain in patients who reach pCR; however, current imaging and biopsy techniques aiming to predict pCR are not accurate enough. This study aims to quantify the residual disease remaining after NST in patients with a favorable response on MRI and residual disease missed with biopsies. METHODS: In the MICRA trial, patients with a favorable response to NST on MRI underwent ultrasound-guided post-NST 14G biopsies followed by surgery. We analyzed pathology reports of the biopsies and the surgical specimens. Primary outcome was the extent of residual invasive disease among molecular subtypes, and secondary outcome was the extent of missed residual invasive disease. RESULTS: We included 167 patients. Surgical specimen showed residual invasive disease in 69 (41%) patients. The median size of residual invasive disease was 18 mm (interquartile range [IQR] 12-30) in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) patients, 8 mm (IQR 3-15) in HR+/HER2-positive (HER2+) patients, 4 mm (IQR 2-9) in HR-negative (HR-)/HER2+ patients, and 5 mm (IQR 2-11) in triple-negative (TN) patients. Residual invasive disease was missed in all subtypes varying from 4 to 7 mm. CONCLUSION: Although the extent of residual invasive disease is small in TN and HER2+ subtypes, substantial residual invasive disease is left behind in all subtypes with 14G biopsies. This may hamper local control and limits adjuvant systemic treatment options. Therefore, surgical excision remains obligatory until accuracy of imaging and biopsy techniques improve.

Short- and long-term outcomes of selective use of Frey or extended lateral pancreaticojejunostomy in chronic pancreatitis.

BACKGROUND: Surgery is the most effective treatment in patients with painful chronic pancreatitis and a dilated pancreatic duct. Studies reporting the outcomes of selected surgical approach according to the pancreatic head size in these patients are lacking. METHOD: This was a retrospective, observational single-centre study of consecutive patients who underwent either a Frey procedure or extended lateral pancreaticojejunostomy (eLPJ) for pain due to chronic pancreatitis with a dilated main pancreatic duct (5 mm or more) between 2006 and 2017. A Frey procedure was used in patients with pancreatic head enlargement (40 mm or more) and eLPJ (full-length pancreaticojejunostomy, including transection of the gastroduodenal artery) in others. A biliodigestive bypass was added in the case of biliary obstruction. RESULTS: Overall, 140 of 220 patients met the eligibility criteria: 70 underwent a Frey procedure and 70 an eLPJ. Hepaticojejunostomy was added in 17.1 per cent of patients (Frey: 24.3 per cent; eLPJ: 10.0 per cent (P = 0.025)). Major morbidity occurred in 15.0 per cent of patients (Frey: 21.4 per cent; eLPJ: 8.6 per cent (P = 0.033)). After a median 7.8 years of follow-up, the mean (s.d.) decrease in Izbicki pain score was 33 (27) points (34 (28) points after a Frey procedure; 32 (26) points after an eLPJ). Pain relief was reported as 'very much' by 87.5 per cent of patients (Frey: 86.1 per cent; eLPJ: 88.9 per cent) and as 'partial' by 11.1 per cent (Frey: 13.8 per cent; eLPJ: 8.3 per cent). CONCLUSION: Selective-use of either a Frey procedure or eLPJ in patients with symptomatic chronic pancreatitis was-associated with low morbidity and long-term pain relief. Adding a-biliodigestive bypass did not increase morbidity.

This house believes that: MARI/TAD is better than sentinel node biopsy after PST for cN+ patients.

The increasing use and effectiveness of primary systemic treatment (PST) enables tailored locoregional treatment. About one third of clinically node positive (cN+) breast cancer patients achieve pathologic complete response (pCR) of the axilla, with higher rates observed in Human Epidermal growth factor Receptor (HER)2-positive or triple negative (TN) breast cancer subtypes. Tailoring axillary treatment for patients with axillary pCR is necessary, as they are unlikely to benefit from axillary lymph node dissection (ALND), but may suffer complications and long-term morbidity such as lymphedema and impaired shoulder motion. By combining pre-PST and post-PST axillary staging techniques, ALND can be omitted in most cN + patients with pCR. Different post-PST staging techniques (MARI/TAD/SN) show low or ultra-low false negative rates for detection of residual disease. More importantly, trials using the MARI (Marking Axillary lymph nodes with Radioactive Iodine seeds) procedure or sentinel lymph node biopsy (SLNB) as axillary staging technique post-PST have already shown the safety of tailoring axillary treatment in patients with an excellent response. Tailored axillary treatment using the MARI procedure in stage I-III breast cancer resulted in 80% reduction of ALND and excellent five-year axillary recurrence free interval (aRFI) of 97%. Similar oncologic outcomes were seen for post-SLNB in stage I-II patients. The MARI technique requires only one invasive procedure pre-NST and a median of one node is removed post-PST, whereas for the SLNB and TAD techniques two to four nodes are removed. A disadvantage of the MARI technique is its use of radioactive iodine, which is subject to extensive regulations.

A clinical perspective on oncoplastic breast conserving surgery.

Breast conserving surgery (BCS) plus radiation treatment is the favored alternative for mastectomy in patients with breast cancer. To allow for breast conservation in patients with large invasive tumors and poor response to neoadjuvant systemic treatment (NST) or patients with extensive ductal carcinoma in situ (DCIS), oncoplastic breast conserving surgery (OPBCS) techniques are introduced. OPBCS allows for breast conservation in a selective group of breast cancer patients who initially would have been treated with mastectomy due to the unfavorable tumor-to-breast ratio. With OPBCS, the oncological tumor excision is combined with plastic surgical breast conservation techniques without compromising oncological safety and maintaining aesthetic outcomes by preserving the shape of the breast. OPBCS should however not be applied to all breast cancer patients and the selection of patients who benefit from OPBCS and the timing of OPBCS are best discussed in a multidisciplinary team (MDT). Caution is required in patients with higher risk of positive margins [e.g., multifocal breast cancer, invasive lobular carcinoma (ILC), larger tumors and DCIS]. In these patients, delayed OPBCS is recommended to facilitate re-excision and maintain excellent breast conserving rates. Despite proven benefits in selected patients, the increase in the adoption of OPBCS is relatively low. This article provides a clinical perspective on OPBCS.