Stem cell markers: A guide to neoadjuvant therapy in breast carcinomas

Aim: This study aims to investigate potential associations between the stem cell population and the degree of tumor regression in breast carcinomas treated with neoadjuvant therapy. Settings and Design: The study included 92 patients with breast carcinoma who received neoadjuvant therapy. Tumor regression was defined based on Miller and Payne grading system. Patients with grade 1 or 2 regression on a 5-point scale were included in group 1 (n = 37), grade 3 regression in group 2 (n = 32), and grade 4 or 5 regression in group 3 (n = 23). Materials and Methods: Immunohistochemical staining was performed on paraffin block sections of every case using CD44, CD24, CD29, CD133, ID4, and ALDH1 antibodies to detect stem cells. Statistical Analysis Used: IBM Statistical Package for the Social Sciences (SPSS), version 23.0 (IBM Corp., Armonk, NY, USA) software was used for statistical analyses, and a P value less than 0.05 was considered statistically significant. Results: Histologically high-grade tumors are more common in the near-complete/complete response group (P = 0.004). HER2-positive tumors were more common in the complete/near-complete response group (P = 0.054). Tumor cells positive for stem cell markers CD44 and CD24 were more common in the poor response group (P = 0.027 and P = 0.001, respectively). CD29 expression was reduced in the posttreatment residual tumor tissue in the near-complete/complete response group. Conclusion: High CD44 and CD24 expression may be a predictor of poor response/nonresponse to neoadjuvant therapy in breast carcinomas. Background: In recent years, stem cells have been defined as the main cell population responsible for resistance to anticancer therapies.

The role of MRI and 18F-FDG PET/CT with respect to evaluation of pathological response in the rectal cancer patients after neoadjuvant chemoradiotherapy

Background: We aimed to evaluate the role of magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography朿omputed tomography (PET-CT) in determining the correct stage and predicting the pathological response. Methods: Seventy one patients with pathologic proven rectal adenocarcinoma, clinical stage IIA-IVA, and neoadjuvant chemoradiotherapy (CRT) were evaluated retrospectively. Radiotherapy was delivered 45� Gy in 25 fractions with concomitant oral capecitabine. Pelvic MRI, colonoscopy, and 18F-FDG PET-CT were performed before the neoadjuvant treatment (NAT). After NAT, MRI and PET-CT were performed for re-evaluation. Results: The median follow-up time was 25 months (range: 3� months). Of the 71 patients who underwent NAT, 57 patients underwent surgery. Downstaging was recorded in 48 (84.2%) of 57 patients who underwent surgery. There was no statistically significant difference between both MRI and PET-CT with pathology results in terms of response evaluation. As a result of the comparison of MRI and PET-CT with pathological results; sensitivity and specificity were 91.6% (44/48) and 22.2% (2/9) for MRI, and 100% (47/47) and 12.5% (1/8) for PET-CT, respectively. Conclusion: PET-CT and MRI are effective in predicting response to NAT and predictive for the pathological response. A more accurate response can be judged when both PET-CT and MRI are executed together in restaging after NAT

Advances in preoperative treatment of colorectal cancer / 中华消化外科杂志

Preoperative treatment of colorectal cancer includes neoadjuvant therapy for initial resectable patients and conversion therapy for initial unresectable patients. In locally advanced rectal cancer, on the basis of neoadjuvant chemoradiotherapy or radiotherapy, increasing the intensity of concurrent chemotherapy, or raising postoperative adjuvant chemotherapy before surgery, or combining with immunotherapy can increase pathological downstaging, contribute to organ preservation, and improve survival of patients. In locally advanced colon cancer, neoadjuvant chemotherapy can improve surgical outcomes. In patients with resectable colorectal liver metastases, neoadjuvant chemotherapy is recommended in patients with unfavorable prognostic factors, but it remains controversial whether it should be combined with targeted therapy. However, in patients with initially unresectable colorectal liver metastases, under the guidance of molecular typing, chemotherapy, especially triple-drug chemotherapy, combined with targeted therapy, is expected to achieve higher objective response rate and convertible rate, thus accepting surgical resection, which improves long-term survival. In addition, for the patients with mismatch repair deficient/micro-satellite instability-high metastatic colorectal cancer, programmed death-1 monoclonal antibody (mAb) and/or cytotoxic T lymphocyte-associated antigen-4 mAb have become the standard first-line treatment option.

Neoadjuvant immunotherapy in microsatellite stability or mismatch repair proficient colorectal cancer / 中华胃肠外科杂志

Immunotherapy has become an important treatment option for microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) colorectal cancer. From late-line to first-line treatment, and even in neoadjuvant setting for early stage colorectal cancer, promising efficacy was observed with immunotherapy. In microsatellite stability (MSS) or mismatch repair proficient (pMMR) colorectal cancer, the researches of neoadjuvant immunotherapy have been conducted constantly. This paper focuses on the recent researches and progress of neoadjuvant immunotherapy for MSS or pMMR colorectal cancer. Neoadjuvant immunotherapy alone led to a good pathological response in a subset of patients. Studies of induction or consolidation immunotherapy before or after neoadjuvant chemoradiotherapy or concurrent immunotherapy during radiotherapy showed higher pathological complete remission (pCR) rates as compared to standard chemoradiotherapy. Studies on sequential dual immunotherapy after radiochemotherapy and targeted therapy combined with neoadjuvant immunotherapy are ongoing. At present, most of these are pilot studies with small sample size. More researches and long-term follow-up are needed to prove the efficacy of neoadjuvant immunotherapy in MSS or pMMR colorectal cancer.

Current status, controversy and challenge in the neoadjuvant immunotherapy of colorectal cancer / 中华胃肠外科杂志

Neoadjuvant therapy for colorectal cancer is widely used in rectal cancer, locally advanced colon cancer, and resectable metastatic and recurrent colorectal cancer. Mismatch repair deficient(dMMR) and microsatellite instablity-high (MSI-H) colorectal cancer patients who benefit from the efficacy of immune checkpoint inhibitors are expected to further improve the efficacy of traditional neoadjuvant therapy based on radiotherapy and chemotherapy. In this paper, the current status of immunotherapy (with emphasis on immune checkpoint inhibitors) is elucidated, and the opportunities of its application in neoadjuvant therapy are analyzed, including poor sensitivity of dMMR tumors to traditional therapy, good immune response of early tumors, predictable, manageable and controllable toxicity of immune checkpoint inhibitors. Colorectal cancer patients have growing and diverse needs to be met. Current controversies and challenges are analyzed, and the future directions are pointed out, including active screening of benefit groups, exploration of efficacy prediction markers, optimization of neoadjuvant immunotherapy models, attention to efficacy evaluation and new therapeutic endpoints. Neoadjuvant therapy should be effective, moderate and accurate based on the treatment target. It is the prerequisite and basis to guarantee medical safety and improve therapeutic effect to attach importance to the standardization and safety of clinical research and to pay attention to patients' interests and legal and ethical demands.

Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors / 中华胃肠外科杂志

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

Background parenchymal enhancement: behavior during neoadjuvant chemotherapy for breast cancer and relationship with a pathological complete response / Realce de fundo do parênquima: comportamento durante quimioterapia neoadjuvante para câncer de mama e relação com resposta patológica completa

Abstract Objective: To evaluate background parenchymal enhancement (BPE) and its characteristics, as well as its behavior before and after neoadjuvant chemotherapy (NAC), in both breasts of patients with unilateral breast cancer. Materials and Methods: This was a retrospective, cross-sectional observational study involving a consecutive sample of women with invasive breast cancer who underwent breast magnetic resonance imaging (MRI) between July 2007 and July 2017, as well as undergoing dynamic contrast-enhanced MRI before and after NAC. In both breasts, we evaluated the BPE in accordance with the Breast Imaging Reporting and Data System. We applied logistic regression analysis, and values of p < 0.05 were considered significant. Results: We evaluated 150 women. The mean age was 45.2 years (range, 20-74 years). The variables correlating independently with a high pre-NAC BPE, in the affected and contralateral breasts, were being under 50 years of age (odds ratio [OR] = 6.55; 95% confidence interval [95% CI]: 2.32-18.46, for both breasts) and a post-NAC BPE reduction (OR = 17.75; 95% CI: 4.94-63.73 and OR = 18.47; 95% CI: 5.19-66.49, respectively). Conclusion: Patients with invasive unilateral breast cancer who have a high pre-NAC BPE in both breasts tend to be under 50 years of age and to show a post-NAC reduction in BPE.

Resumo Objetivo: Avaliar o realce de fundo do parênquima (RFP), suas características e seu comportamento pré- e pós-quimioterapia neoadjuvante (QTN) em ambas as mamas em pacientes com câncer de mama unilateral. Materiais e Métodos: Estudo observacional transversal retrospectivo realizado em um serviço acadêmico e um centro especializado em mamas, que incluiu mulheres com câncer de mama invasivo submetidas a QTN e que realizaram exames de ressonância magnética (RM) das mamas com contraste antes e depois da quimioterapia, entre julho de 2007 e julho de 2017. Os exames foram realizados de acordo com protocolo padronizado. O RFP foi avaliado em ambas as mamas de acordo com o ACR BI-RADS, 5ª edição. Foi aplicada análise de regressão logística. O nível de significância adotado para os testes estatísticos foi p < 0,05. Resultados: Foram analisadas 150 mulheres. A idade média foi de 45,2 anos (20-74 anos). Na análise de regressão multivariada, apenas a idade inferior a 50 anos e redução do RFP correlacionaram-se independentemente com o nível alto de RFP em ambas as mamas: mamas afetadas (odds ratio [OR]: 6,55; intervalo de confiança 95% [IC 95%]: 2,32-18,46 e OR: 17,75; IC 95%: 4,94-63,73, respectivamente); mamas contralaterais (OR: 6,55; IC: 95% 2,32-18,46 e OR: 18,47; IC 95%: 5,19-66,49, respectivamente). Conclusão: Idade abaixo de 50 anos e redução do RFP pós-QTN correlacionaram-se independentemente com maior RFP pré-QTN em ambas as mamas em pacientes com câncer de mama invasivo unilateral submetidas a QTN.

Predictive factors for tumour response after the neoadjuvant-treatment of rectal adenocarcinoma / Fatores preditivos de resposta tumoral após tratamento neoadjuvante de adenocarcinoma retal

ABSTRACT Purpose Standard of care for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. This study identified predictive factors for tumour response in our series. Patients and methods Between January 2005 and December 2018, 292 patients with locally advanced rectal cancer treated by preoperative chemo-radiation before surgery were retrospectively analyzed. The radiation dose was 50.4 Gy with fluoropyrimidine-based chemotherapy regimens. Patients-tumour and treatment-factors were tested for influence on tumour down staging and regression grade using Mandard scoring system on surgical specimens (TRG). Results Median age was 69 years (range 39-87); 33.9% of patients was Stage II and 54.5% Stage IIIB. Tumour down staging occurred in 211 patients (73%), including 63 patients (21.6%) with ypT0 (documented T0 at surgery) and 148 patients (50.7%) with a satisfactory tumour regression grade defined as TRG2­3. Upper rectal tumours were identified to predictive factors for pathologic complete response by univariate analysis (p = 0.002). TRG1­3 was associated with intervals from chemo-radiation to surgery (p = 0.004); TRG1­3 rates were higher with longer intervals: 1.71% in ≤ 5 weeks, 23.63% in 6-8 weeks and 46.9% in ≥ 9 weeks; and PTV 50.4 ≥ 800cc (p = 0.06); 3 and 5 years survivals were 85% and 90% for the group as a whole. Among ypT0 cases, the overall survival was 91.1% without significantly different (p = 0.25) compared with the remaining group, 87.2%. Among ypT0 cases, the relapse-free survival was 94.5%, with significantly different (p = 0.03) compared with the remaining group 78.2%. There were no treatment-associated fatalities. Thirty-two patients (10.96%) experienced Grade III/IV toxicities (proctitis, ephitelitis and neutropenia). Conclusions Tumour localization was identified as predictive factors of pathologic complete response for locally advanced rectal cancer treated with preoperative chemo-radiation. Upper rectal tumours are more likely to develop complete responses. Delay in surgery was identified as a favorable predictive factor for TRG1­3. The relapse-free survival in pathologic complete response group was higher compared with non-pathologic complete response.

RESUMO Objetivo O tratamento padrão para o câncer retal localmente avançado é a quimiorradioterapia neoadjuvante, seguida de cirurgia. Este estudo identificou fatores preditivos de resposta tumoral em nossa série. Pacientes e métodos Entre janeiro de 2005 e dezembro de 2018, 292 pacientes com câncer retal localmente avançado, tratados com quimiorradiação pré-operatória, foram retrospectivamente analisados. O tratamento quimioterápico foi à base de fluoropirimidina e a dose de radiação foi de 50,4 Gy. Os tumores dos pacientes e os fatores do tratamento foram testados quanto à influência no estadiamento do tumor e no grau de regressão usando o sistema de classificação de Mandard em espécimes cirúrgicos (TRG). Resultados A mediana das idades foi 69 anos (variação de 39 a 87); 33,9% dos pacientes estavam no estágio II e 54,5% no estágio IIIB. O estadiamento do tumor ocorreu em 211 pacientes (73%), incluindo 63 pacientes (21,6%) com ypT0 (T0 documentado na cirurgia) e 148 pacientes (50,7%) com grau satisfatório de regressão do tumor, definido como TRG1­3. Os tumores retais superiores foram identificados como fatores preditivos de resposta patológica completa por análise univariada p = 0,002. TRG1­3 foi associado aos intervalos entre a quimioterapia e a cirurgia p = 0,004; As taxas de TRG1­3 foram maiores com intervalos mais longos: 1,71% em ≤ 5 semanas, 23,63% em 6-8 semanas e 46,9% em ≥ 9 semanas; e PTV 50,4 ≥ 800cc (p = 0,06); as sobrevidas de 3 e 5 anos foram de 85% e 90% para o grupo em geral. Entre os casos de ypT0, a sobrevida global foi de 91,1%, sem diferença significativa (p = 0,25) na comparação com o grupo restante (87,2%). Entre os casos de ypT0, a sobrevida livre de recidiva foi de 94,5%, com diferença significativa (p = 0,03) na comparação com o grupo restante (78,2%). Não houve fatalidades associadas ao tratamento. Trinta e dois pacientes (10,96%) apresentaram toxicidade de grau III/IV (proctite, efitelite e neutropenia). Conclusões A localização do tumor foi identificada como fator preditivo de resposta patológica completa para o câncer retal localmente avançado tratado com quimiorradiação pré-operatória. Os tumores retais superiores têm mais probabilidade de desenvolver respostas completas. O atraso da cirurgia foi identificado como um fator preditivo favorável para o TRG1­3. A sobrevida livre de recidiva no grupo com resposta patológica completa à quimiorradioterapia pré-operatória foi maior comparado ao grupo com resposta patológica incompleta.

Analysis of recurrence pattern of neoadjuvant therapy combined with surgical treatment for esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective To evaluate the recurrence pattern and identify the risk factors of esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Methods Clinical data of 275 patients with thoracic esophageal squamous cell carcinoma treated with neoadjuvant therapy combined with surgery from December 2011 to December 2015 were retrospectively analyzed.The follow-up data of the enrolled patients were complete and analyzable.The recurrence pattern,recurrence time,recurrence location and influencing factors after neoadjuvant therapy in combination with surgery were analyzed.The recurrence rate was calculated by Kaplan-Meier method.The multivariate analysis was performed by Cox regression model.Results The median follow-up time was 32 (3-84) months,and the median time of the first recurrence was 10.6(2.0-69.1) months.The 1-,2-and 3-year recurrence rates were 32.0％,45.1％ and 52.3％,respectively.A total of 152 cases (55.3％) had recurrence.Among them,77 cases (50.6％) had local-regional recurrence (LRR),34 cases (23.4％) had distant metastasis (DM),33 cases (21.7％) had LRR+DM and 8 cases (6.0％) had recurrence in unknown site.Among the patients with LRR,lymph node recurrence was the most common (n =98,89.1％).For DM patients,lung metastasis (n =33,49.3％),liver metastasis (n=16,23.9％),bone metastasis (n=14,20.9％) and non-regional lymph node metastasis (n=14,20.9％) were commonly observed.The multivariate analysis showed that postoperative T stage (P=0.008),N stage (P＜0.001) and the number of lymph node dissection (P＜0.001) were the independent risk factors for recurrence after treatment.Conclusions The recurrence rate after neoadjuvant therapy remains relatively high for esophageal squamous cell carcinoma,and the regional lymph node is the most common site of recurrence.Postoperative pathological T staging,N staging and the number of lymph node dissection are the independent risk factors for recurrence after treatment.

Prognostic analysis of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgical treatment / 中华放射肿瘤学杂志

Objective To evaluate the clinical efficacy and prognostic factors of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Methods From December 2011 to December 2015,152 cases of recurrent thoracic esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery were retrospectively analyzed.The overall survival (OS) after treatment failure,clinical efficacy and prognostic factors of different salvage treatments were analyzed.OS was calculated by Kaplan-Meier method.Prognostic analysis was performed by using multivariate Cox regression model.Results The median interval of the first recurrence was 10.6(2.0 to 69.1) months.The median OS after recurrence was 8.0(0.8 to 43.3) months.The 1-,2-and 3-year OS rates after recurrence were 36.0％,15.1％ and 5.2％,respectively.The median OS of patients with locoregional recurrence alone,distant metastasis alone and locoregional recurrence combined with distant metastasis was 11.3(1.8 to 43.3) months,6.7(1.2 to 28.6) months and 5.1 (0.8 to 22.9) months,respectively.Multivariate analysis demonstrated that neoadjuvant chemotherapy (P=0.009),ypTNM stage (P=0.012),comprehensive treatment after recurrence (P=0.000) and locoregional recurrence (P=0.026) were independently correlated with the OS of patients with recurrent esophageal squamous cell carcinoma.Conclusions Neoadjuvant therapy,ypTNM stage,recurrence pattern and postrecurrence treatment are the independent risk factors for clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy is not satisfactory.After recurrence,combined treatment mode should be adopted according to the site of recurrence and neoadjuvant treatment mode to maximize the benefits of salvage treatment.

Consensus on the Watch and Wait policy in rectal cancer patients after neoadjuvant treatment (2020 version) / 中华胃肠外科杂志

Patients with clinical complete response(cCR) after neoadjuvant treatment receiving the Watch and Wait('W&W’) policy can achieve similar survival of those with yeild pathological complete response (ypCR), and have significantly improved quality of life compared to those undergoing radical operation. Based on thoroughly reviewing the literatures and guidelines at home and abroad, and referring associated clinical experiences from a lot of domestic medical centers, the present version of Chinese Consensus on W&W was established by a panel of many experts of gastrointestinal surgery, medical oncology, radiation oncology, pathology, endoscopy, radiology. This consensus mainly elucidates important conceptions of the W&W policy, current key evidences, risks and benefits for patients, conditions to carry out W&W, criteria of cCR diagnosis, timing of evaluation, follow - up plan, salvage treatment for local relapse and distant metastasis, associated problems of local resection, and is expected to facilitate the clinical practice and research of W&W policy in China.

Prognostic analysis of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgical treatment / 中华放射肿瘤学杂志

Objective@#To evaluate the clinical efficacy and prognostic factors of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.@*Methods@#From December 2011 to December 2015, 152 cases of recurrent thoracic esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery were retrospectively analyzed. The overall survival (OS) after treatment failure, clinical efficacy and prognostic factors of different salvage treatments were analyzed. OS was calculated by Kaplan-Meier method. Prognostic analysis was performed by using multivariate Cox regression model.@*Results@#The median interval of the first recurrence was 10.6(2.0 to 69.1) months. The median OS after recurrence was 8.0(0.8 to 43.3) months. The 1-, 2-and 3-year OS rates after recurrence were 36.0%, 15.1% and 5.2%, respectively. The median OS of patients with locoregional recurrence alone, distant metastasis alone and locoregional recurrence combined with distant metastasis was 11.3(1.8 to 43.3) months, 6.7(1.2 to 28.6) months and 5.1(0.8 to 22.9) months, respectively. Multivariate analysis demonstrated that neoadjuvant chemotherapy (P=0.009), ypTNM stage (P=0.012), comprehensive treatment after recurrence (P=0.000) and locoregional recurrence (P=0.026) were independently correlated with the OS of patients with recurrent esophageal squamous cell carcinoma.@*Conclusions@#Neoadjuvant therapy, ypTNM stage, recurrence pattern and post-recurrence treatment are the independent risk factors for clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery. Clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy is not satisfactory. After recurrence, combined treatment mode should be adopted according to the site of recurrence and neoadjuvant treatment mode to maximize the benefits of salvage treatment.

Nomogram for accurate prediction of breast and axillary pathologic response after neoadjuvant chemotherapy in node positive patients with breast cancer

PURPOSE: Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. METHODS: We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. RESULTS: Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84–0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837–0.869). CONCLUSION: Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.

The Benefit of Post-Mastectomy Radiotherapy in ypN0 Patients after Neoadjuvant Chemotherapy According to Molecular Subtypes / 한국유방암학회지

PURPOSE: The benefit of post-mastectomy radiation therapy (PMRT) in patients with breast cancer who achieve ypN0 following neoadjuvant chemotherapy (NAC) has not yet been established. This study aimed to identify the role of PMRT in patients who achieve ypN0 according to molecular subtype. METHODS: We identified patients initially suspected with axillary disease who achieved ypN0 following NAC. From 13 institutions of the Korean Radiation Oncology Group between 2005 and 2011, a total of 189 patients were included in the analysis. Effects of PMRT on loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) were evaluated for different molecular subtypes. RESULTS: In all patients, the prognostic effect of PMRT on LRC, DFS, or OS was not significant. Subgroups analysis showed that the effect of PMRT on LRC was different according to molecular subtype (p for interaction = 0.019). PMRT was associated with greater LRC in the luminal subtype (p = 0.046), but not in other subtypes. CONCLUSION: In patients who achieve ypN0 following NAC and mastectomy, PMRT shows no additional survival benefits for any molecular subtype.

Efficacy and Feasibility of Adding Induction Chemotherapy to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Phase II Clinical Trial

PURPOSE: Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer. METHODS: This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3–4 and/or N1–2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45–50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary end-points, respectively. RESULTS: The study participants included 37 males and 17 females, with a median age of 59 years (range, 20–80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent. CONCLUSION: The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.

Oncological outcomes in extended time intervals between preoperative chemoradiotherapy with capecitabine and surgery in operable rectal adenocarcinoma / Resultados oncológicos en intervalos extendidos de tiempo entre quimioradioterapia preoperatoria con capecitabina y cirugía en adenocarcinoma rectal operable

Objective: To assess whether extended time intervals (8-12, 13-20 and >20 weeks) between the end of neoadjuvant chemoradiotherapy and surgery affect overall survival, disease-free survival. Materials and methods: Retrospective study in 120 patients with rectal adenocarcinoma without evidence of metastasis (T1-4/N0-2/M0) at the time of diagnosis that underwent surgery with curative intent after neoadjuvant chemoradiotherapy with capecitabine and obtained R0 or R1 resection between January 2010 to December 2014 at the National Cancer Institute of Peru. Dates were evaluated by Kaplan-Meier method, log- rank test and Cox regression analysis. Results: Of the 120 patients, 70 were women (58%). The median age was 63(26-85) years. All received neoadjuvant chemoradiotherapy. No significant difference was found between the association of the median radial (0.6, 0.7 and 0.8 cm; p=0.826) and distal edge (3.0, 3.5 and 4.0 cm; p=0.606) with time interval groups and similarly the mean resected (18.8, 19.1 and 16.0; p=0.239) and infiltrated nodules (1.05, 1.29 and 0.41); p=0.585). The median follow-up time of overall survival and desease free survival was 40 and 37 months, respectively. No significant differences were observed in overall survival (79.0%, 74.6% and 71.1%; p=0.66) and disease-free survival (73.7%, 68.1% and 73.6%; p=0.922) according to the three groups studied at the 3-year of follow-up. Conclusions: We found that widening the time intervals between the end of neoadjuvant chemoradiotherapy and surgery at 24 weeks does not affect the overall survival, disease-free survival and pathological outcomes. It allows to extend the intervals of time for future studies that finally will define the best time interval for the surgery

Objetivo: Evaluar si los intervalos de tiempo extendidos (8-12, 13-20 y >20 semanas) entre el fin de la quimioradioterapia neoadyuvante y la cirugía afectan la sobrevida global, y la sobrevida libre de enfermedad. Material y métodos: Estudio retrospectivo de 120 pacientes con adenocarcinoma rectal sin evidencia de metástasis (T1-4/N0-2/M0) al momento del diagnóstico que se sometieron a cirugía con intención curativa luego de quimioradioterapia neoadyuvante con capecitabina y tuvieron resección R0 o R1 entre enero 2010 y diciembre 2014 en el Instituto Nacioanal de Enfermedades Neoplásicas de Perú. El análisis se hizo con el método de Kaplan-Meier, la prueba log-rank y la regresión de Cox. Resultados: De 120 pacientes, 70 fueron mujeres (58%). La mediana de la edad fue 63 años (26-85 años). Todos recibieron quimioradioterapia neoadyuvante. No hubo diferencia significativa entre la asociación de las medianas de los bordes radial (0,6, 0.7 y 0,8 cm; p=0,826) y distal (3,0, 3,5 y 4,0 cm; p=0,606) con los intervalos de tiempo de los grupos y similarmente con la media de los ganglios resecados (18,8, 19,1 y 16,0; p=0,239) e infiltrados (1,05, 1,29 y 0,41; p=0,585). No se observaron diferencias significativas en sobrevida global (79,0%, 74,6% y 71,1%; p=0,66) y sobrevida libre de enfermedad (73,7%, 68,1% y 73,6%; p=0,922), en los tres grupos estudiados a 3 años de seguimiento. Conclusiones: Encontramos que aumentar los intervalos de tiempo entre el fin de la quimioradioterapia neoadyuvante y la cirugía hasta 24 semanas no afecta la sobrevida global, sobrevida libre de enfermedad ni los desenlaces patológicos. Esto permitiría extender los intervalos de tiempo en estudios futuros para definir el mejor intervalo de tiempo para la cirugía

Negative peritoneal washing cytology during interval debulking surgery predicts overall survival after neoadjuvant chemotherapy for ovarian cancer / 부인종양

OBJECTIVE: Optimal debulking in interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) has been reported as a prognostic factor for patients with ovarian cancer. However, the identification of microscopic residual disease (MRD) using visualization and palpation is subjective. Peritoneal washing cytology (PWC) during IDS is an easy-to-implement, objective approach for assessing disease status, although its clinical relevance and association with MRD is not known. The aim of this study was to evaluate the efficacy of PWC during IDS. METHODS: In total, 164 patients diagnosed with ovarian cancer at our institution were retrospectively evaluated, including 64 who had received NAC. Seventeen patients had undergone an exploratory laparotomy followed by NAC, while the remaining patients were diagnosed based on imaging, peritoneal cytology, and tumor markers. The PWC was performed before intraperitoneal observation at laparotomy during IDS. RESULTS: NAC-treated patients had stage III–IV disease. IDS was performed in 78.1% of NAC-treated patients. Seventeen patients (26.6%) were PWC-negative and 33 patients (51.6%) were PWC-positive. Fourteen patients (21.9%) had progressive disease and were ineligible for IDS. The median overall survival of the PWC-negative, PWC-positive, and non-IDS groups was 47, 18, and 5 months, respectively. The differences were significant (p < 0.01). PWC was an independent prognostic factor in the multivariate Cox regression analysis (p < 0.001). CONCLUSION: PWC during IDS may be a prognostic factor for NAC-treated patients with ovarian cancer. PWC may be more useful than visualization and palpation in IDS for determining the presence of MRD.

Effect of denosumab combined with surgery on sacral giant cell tumor / 肿瘤研究与临床

Objective To evaluate the clinical benefits of denosumab in treatment of sacral giant cell tumor of bone(GCTB) when used preoperatively or postoperatively along with surgery, and to analysis the improvement of sacral nerve function. Methods Thirty patients diagnosed as sacral GCTB in Musculoskeletal Tumor Center of Peking University People's Hospital from April 2014 to July 2016 were divided into control group (10 cases), post-operative group (9 cases), and neoadjuvant group (11 cases). Patients in the post-operative and neoadjuvant group were treated with 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle. Results Three patients in the control cohort 1 had recurrence (3/10), no recurrence occurred in the post-operative group (0/9), and 3 patients in the neoadjuvant group had recurrence(3/11).There were no significant differences in event-free survival(EFS) among the three groups (P = 0.133). The objective response rate (OTR) was 63.6 % (7/11) in the neoadjuvant group based on the RECIST 1.1 criteria for evaluating the efficacy of solid tumors. Five cases had significant pain improvement (defined 2 points improved) and had much better bladder and bowel functions. Four patients were able to have their indwelling catheters removed after neoadjuvant denosumab treatment. Conclusions Neoadjuvant therapy with denosumab can relieve the symptoms and neurologic deficits caused by nerve compression and can diminish the intraoperative blood loss. Surgical removal of the tumor is still the basic treatment of sacral GCTB.

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial

PURPOSE: Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. METHODS: This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m2 intravenously on day 1 plus oral capecitabine 825 mg/m2 twice daily during LDRBT and EBRT. RESULTS: The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. CONCLUSION: A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

Efficacy of Imatinib Mesylate Neoadjuvant Treatment for a Locally Advanced Rectal Gastrointestinal Stromal Tumor

Surgery is the standard treatment for a primary gastrointestinal stromal tumor (GIST); however, surgical resection is often not curative, particularly for large GISTs. In the past decade, with imatinib mesylate (IM), management strategies for GISTs have evolved significantly, and now IM is the standard care for patients with locally advanced, recurrent or metastatic GISTs. Adjuvant therapy with imatinib was recently approved for use, and preoperative imatinib is an emerging treatment option for patients who require cytoreductive therapy. IM neoadjuvant therapy for primary GISTs has been reported, but there is no consensus on the dose of the drug, the duration of treatment and the optimal time of surgery. These are critical because drug resistance or tumor progression can develop with a prolonged treatment. This report describes two cases of large rectal malignant GISTs, for which a abdominoperineal resection was initially anticipated. The two patients received IM preoperative treatment; we followed-up with CT or magnetic resonance imaging to access the response. After 9 months of treatment, a multi-disciplinary consensus that maximal benefit from imatinib had been achieved was reached. We determined the best time for surgical intervention and successfully performed sphincter-preserving surgery before resistance to imatinib or tumor progression occurred. We believe that a multidisciplinary team approach, considerating the optimal duration of therapy and the timing of surgery, is required to optimize treatment outcome.