Comparative study of weekly and three-weekly neoadjuvant carboplatin in triple-negative breast cancer: retrospective analysis in real-world settings.

PURPOSE: Tri-weekly carboplatin is an established neoadjuvant treatment for triple-negative breast cancer, enhancing pathological complete response (pCR) and overall survival. This study explores if weekly carboplatin provides lower toxicity and comparable pCR rates. METHODS/PATIENTS: A retrospective multicenter study (January 2021 to March 2023) compares outcomes of weekly and tri-weekly carboplatin. RESULTS: Among 104 participants, 60% received weekly and 40% tri-weekly treatments. Weekly administration had fewer discontinuations (56.5 vs. 70.7%, p = 0.154). Both schedules exhibited similar overall toxicity (p = 0.087), with slightly higher grade 3-4 toxicity in the tri-weekly group (56.1 vs. 48.4%, p = 0.126). Hematological toxicity was comparable, but the weekly group experienced more diarrhea (p = 0.432) and asthenia (p = 0.012). Weekly treatment correlated with more frequent breast-conserving surgeries (p = 0.004). pCR rates were 50% with weekly and 61% with tri-weekly regimens (p = 0.186). CONCLUSIONS: Weekly carboplatin exhibited comparable toxicity, a trend toward fewer interruptions, and similar pCR rates. Prospective studies are essential for validating these findings.

Interdisciplinary Spanish consensus on a watch-and-wait approach for rectal cancer.

Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.

Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience.

PURPOSE: Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. MATERIALS AND METHODS: In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. RESULTS: Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0-1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1-2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. CONCLUSIONS: Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status.

A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait.

BACKGROUND: Neoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCT compared to fluoropirimidine alone regimens in terms of primary tumor response remains unclear. Since oxalipatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine + oxaliplatin) for patients with distal rectal cancer. METHODS: In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54 Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine + oxaliplatin. Magnetic resonance(MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1 cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy(RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) may be enrolled in an organ-preservation program(WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Secondary endpoints are 3-year surgery-free survival, TME-free survival, distant metastases-free survival, local regrowth-free survival and colostomy-free survival. DISCUSSION: Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05000697; registered on August 11th, 2021.

Technical Implications for Surgical Resection in Locally Advanced Pancreatic Cancer.

Pancreatic ductal adenocarcinoma remains a global health challenge and is predicted to soon become the second leading cause of cancer death in developed countries. Currently, surgical resection in combination with systemic chemotherapy offers the only chance of cure or long-term survival. However, only 20% of cases are diagnosed with anatomically resectable disease. Neoadjuvant treatment followed by highly complex surgical procedures has been studied over the last decade with promising short- and long-term results in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). In recent years, a wide variety of complex surgical techniques that involve extended pancreatectomies, including portomesenteric venous resection, arterial resection, or multi-organ resection, have emerged to optimize local control of the disease and improve postoperative outcomes. Although there are multiple surgical techniques described in the literature to improve outcomes in LAPC, the comprehensive view of these strategies remains underdeveloped. We aim to describe the preoperative surgical planning as well different surgical resections strategies in LAPC after neoadjuvant treatment in an integrated way for selected patients with no other potentially curative option other than surgery.

PD-L1 expression in gastric and gastroesophageal junction cancer patients treated with perioperative chemotherapy.

BACKGROUND AND OBJECTIVES: The incidence, predictive, and prognostic impact of programmed cell death (PD-L1) expression in gastric (GC) and gastroesophageal junction tumors (GEJC) treated with perioperative chemotherapy is poorly understood. We aimed to assess PD-L1 expression by immunohistochemistry (IHC) in both pre and posttreatment specimens evaluating its impact on pathological response and survival outcomes. METHODS: Retrospective cohort of patients with GC and GEJ tumors treated in a single western cancer center between 2007 and 2017. PD-L1 expression was assessed by IHC before and after neoadjuvant chemotherapy, in surgical samples, and reported as combined positive score (CPS). CPS > 1% was tested for its association with pathological response and overall survival (OS). RESULTS: We were able to assess PD-L1 expression in at least one tissue sample from 155 subjects. PD-L1 positivity rate was 20%. In 74 paired samples, a 21% discordance between PD-L1 expression in biopsy sample and surgical specimen was observed. With a median follow-up period of 60.3 months, 5-years disease-free survival was 60.5% with a median OS not reached. PD-L1 expression was neither associated with pathological response or survival outcomes. CONCLUSIONS: PD-L1 expression in the setting of locally advanced GC tumors was relatively low and can vary considering the tissue sample analyzed. This expression had no association with survival or pathological response in this population.

Quality of life in a randomized trial comparing two neoadjuvant regimens for locally advanced rectal cancer-INCAGI004.

BACKGROUND: Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC), but the emergence of different drug regimens may result in different response rates. Good clinical response translates into greater sphincter preservation, but quality of life (QOL) may be impaired after treatment due to chemoradiotherapy and surgical side effects. OBJECTIVE: To prospectively evaluate the impact of clinical response and surgical resection on QOL in a randomized trial comparing two different neoCRT regimens. METHODS: Stage II and III rectal cancer patients were randomized to receive neoCRT with either capecitabine (group 1) or 5-Fu and leucovorin (group 2) concomitant to long-course radiotherapy. Clinical downstaging was accessed using MRI 6-8 weeks after treatment. EORTCs QLQ-C30 and CR38 were applied before treatment (T0), after neoCRT (T1), after rectal resection (T2), early after adjuvant chemotherapy (T3), and 1 year after the end of treatment or stoma closure (T4). The Wexner scale was used for fecal incontinence evaluation at T4. A C30SummaryScore (Geisinger and cols.) was calculated to compare QOL results. RESULTS: Thirty-two patients were assigned to group 1 and 31 to group 2. Clinical downstaging occurred in 70.0% of group 1 and 53.3% of group 2 (p = 0.288), and sphincter preservation was 83.3% in group 1 and 80.0% in group 2 (p = 0.111). No significant difference in QOL was detected when comparing the two treatment groups after neoCRT using QLQ-C30. However, the CR38 module detected differences in micturition problems (15.3 points), gastrointestinal problems (15.3 points), defecation problems (11.8 points), and sexual satisfaction (13.3 points) favoring the capecitabine group. C30SummaryScore detected significant improvement comparing T0 to T1 and deterioration comparing T1 to T2 (p = 0.025). The mean Wexner scale score was 9.2, and a high score correlated with symptoms of diarrhea and defecation problems at T4. CONCLUSIONS: QOL was equivalent between groups after neoCRT except for micturition problems, gastrointestinal problems, defecation problems, and sexual satisfaction favoring the capecitabine arm after. The overall QOL using the C30SummaryScore was improved after neoCRT, but decreased following rectal resection, returning to basal levels at late evaluation. Fecal incontinence was high after sphincter preservation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03428529.

Comparative Effectiveness of Total Neoadjuvant Therapy Versus Standard Adjuvant Chemotherapy for Locally Advanced Rectal Cancer.

INTRODUCTION: The use of total neoadjuvant therapy (TNT) for locally advanced rectal cancer has been increasing in recent years, but the long-term overall survival characteristics of this approach is currently unknown. METHODS: We performed a retrospective study of patients with clinical stage II/III rectal cancer within the National Cancer Database. Patients who received TNT (defined as chemotherapy, followed by CRT, followed by surgery) were propensity score matched to patients who received adjuvant therapy (defined as CRT, followed by surgery, followed by chemotherapy). We compared overall survival (OS) and rates of pathologic complete response (pCR) between the 2 arms. RESULTS: Of the 4300 patients in our cohort, 3502 (81%) received adjuvant therapy and 798 (19%) received TNT. At baseline, patients who received TNT were more likely to have higher clinical T and N stages (P< .001). The 5-year OS was 77% for both TNT and adjuvant therapy patients (hazard ratio [HR] 1.06, 95% confidence interval [CI], 0.88-1.28, P = .57). After propensity score matching and adjusting for potential confounders, there were no significant differences in OS (HRadj 1.00, 95% CI, 0.71-1.40, P = .99). After propensity score matching, there were higher pCR rates among TNT patients (16.1%) compared to adjuvant therapy patients (12.0%) (P = .037). CONCLUSION: In this observational study, we found TNT was not associated with a lower OS compared to standard adjuvant chemotherapy. This finding potentially reassures clinicians choosing TNT as an alternative to adjuvant chemotherapy. However, future prospective data are needed to confirm these findings.

Analysis of long-term oncological results of clinical versus pathological responses after neoadjuvant treatment in locally advanced rectal cancer.

BACKGROUND: Nonoperative management after neoadjuvant treatment in low rectal cancer enables organ preservation and avoids surgical morbidity. Our aim is to compare oncological outcomes in patients with clinical complete response in watch and wait strategy with those who received neoadjuvant therapy followed by surgery with a pathological complete response. METHODS: Patients with non-metastatic rectal cancer after neoadjuvant treatment with clinical complete response in watch and wait approach (group 1, n = 26) and complete pathological responders (ypT0N0) after chemoradiotherapy and surgery (group 2, n = 22), between January 2011 and October 2018, were included retrospectively, and all of them evaluated and followed in a multidisciplinary team. A comparative analysis of local and distant recurrence rates and disease-free and overall survival between both groups was carried out. Statistical analysis was performed using log-rank test, Cox proportional hazards regression model, and Kaplan-Meier curves. RESULTS: No differences were found between patient's demographic characteristics in both groups. Group 1: distance from the anal verge mean 5 cm (r = 1-12), 10 (38%) stage III, and 7 (27%) circumferential resection margin involved. The median follow-up of 47 months (r = 6, a 108). Group 2: distance from the anal verge mean 7 cm (r = 2-12), 16 (72%) stage III, and 13 (59%) circumferential resection margin involved. The median follow-up 49.5 months (r = 3, a 112). Local recurrence: 2 patients in group 1 (8.3%) and 1 in group 2 (4.8%) (p = 0.6235). Distant recurrence: 1 patient in group 1 (3.8%) and 3 in group 2 (19.2%) (p = 0.2237). Disease-free survival: 87.9% in group 1, 80% in group 2 (p = 0.7546). Overall survival: 86% in group 1 and 85% in group 2 (p = 0.5367). CONCLUSION: Oncological results in operated patients with pathological complete response were similar to those in patients under a watch and wait strategy mediating a systematic and personalized evaluation. Surgery can safely be deferred in clinical complete responders.

Do We Have to Treat All T3 Rectal Cancer the Same Way?

Chemoradiotherapy (CRT) followed by surgery is the recommended approach in the last years for stage II and III rectal cancer with the intention to decrease the risk of local recurrence. However, fewer patients benefit from this strategy in terms of overall survival and long-term adverse outcomes because T3 rectal cancer has a broad range of prognosis, as shown by recent publications. Many patients with cT3 rectal cancer have a substantial risk of overtreatment with long-term toxicity related to radiotherapy that could be avoided in a subset group of cT3 tumors with good prognosis. These findings raised the question of whether all cT3 rectal cancer should receive preoperative radiotherapy and if a selected cT3 subgroup could be treated by surgery alone. This review addresses the rationale of selecting good prognosis cT3 rectal cancer for surgery alone and analyzes the data to support this recommendation.

Background parenchymal enhancement: behavior during neoadjuvant chemotherapy for breast cancer and relationship with a pathological complete response.

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.

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 (20­74 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%]: 2,32­18,46 e OR: 17,75; IC 95%: 4,94­63,73, respectivamente); mamas contralaterais (OR: 6,55; IC: 95% 2,32­18,46 e OR: 18,47; IC 95%: 5,19­66,49, 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.

Marking axillary nodes with 4% carbon microparticle suspension before neoadjuvant chemotherapy improves sentinel node identification rate and axillary staging.

BACKGROUND AND OBJECTIVES: Marking positive lymph nodes (LNs) before neoadjuvant chemotherapy (NAC) may improve the accuracy of sentinel lymph node biopsy (SLNB). The aim of this study was to determine the feasibility of marking LNs with 4% carbon microparticle suspension (CMS) before NAC and to evaluate if this technique would improve the SLNB identification rate. METHODS: A prospective study of patients with cT1-T4, cN1-N2 breast cancer who underwent US-guided fine-needle aspiration biopsy (FNAB) of suspected LNs and concomitant marking with 4% CMS was performed. After NAC, LNs marked with 4% CMS and those marked with Patent Blue V dye (PBV) were identified and resected. RESULTS: Of the 123 patients included, 74 (60.1%) had positive LNs at FNAB. During axillary surgery, 4% CMS was identified in 121 of 123 patients (98.3%) and blue sentinel LNs in 91% (112 of 123 patients) (P = .0103). Comparing isolated results of PBV and 4%CMS + PBV, the association was better in identifying positive LNs (72.2% vs 97.7%) (P = .02). CONCLUSION: The association of 4% CMS and PBV is feasible and significantly increased the identification rate of positive LNs. 4% CMS may play an important role as a complementary technique in patients submitted to NAC.

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.

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.

Does neoadjuvant therapy for pancreatic head adenocarcinoma increase postoperative morbidity? A systematic review of the literature with meta-analysis.

Neoadjuvant treatment (NT) for pancreatic head cancer may allow some patients to undergo curative resection, but its impact on postoperative complications remains unclear. A systematic review and meta-analysis were performed to compare overall postoperative morbidity, pancreatic fistula, and mortality between patients who underwent upfront surgery and those who underwent neoadjuvant therapy first. Forty-five studies with 3359 patients were included. No significant differences in morbidity and mortality rates associated with NT for pancreatic head cancer were detected in this study.

New standard in locally advanced rectal cancer.

In the following review we intend to ascertain the optimal neoadjuvant therapy in patients with locally advanced rectal cancer. In 2004, a study revealed that chemoradiotherapy (CRT) resulted in better local control when performed preoperatively rather than postoperatively, thus neoadjuvant treatment was established as a standard treatment. Subsequently, the Polish study and the Trans-Tasman Radiation Oncology Group showed no statistically significant difference between concomitant CRT over 5 wk vs short-course radiotherapy (RT). Therefore, both were established as standard neoadjuvant treatments. Later, the Stockholm III study demonstrated that short-course RT had a higher complete pathological response than long-course RT. It also showed that a delay between RT and surgery presented fewer complications. This opened a window of time to provide an early and effective systemic treatment to prevent distant metastases. Studies show that short-course RT plus oxaliplatin-based chemotherapy could achieve this. When comparing this total neoadjuvant treatment (TNT) vs concomitant CRT, the former showed greater complete pathological response and lower acute toxicity. Studies presented during 2020 have also shown the benefits of TNT in terms of complete pathological response, as well as disease and metastasis-free survival. Our review suggests that probably TNT should be the new standard treatment for these patients. However, we will have to wait for the full text publications of these studies to confirm this statement.

Rab5C enhances resistance to ionizing radiation in rectal cancer.

Rectal cancer represents one third of the colorectal cancers that are diagnosed. Neoadjuvant chemoradiation is a well-established protocol for rectal cancer treatment reducing the risk of local recurrence. However, a pathologic complete response is only achieved in 10-40% of cases and the mechanisms associated with resistance are poorly understood. To identify potential targets for preventing therapy resistance, a proteomic analysis of biopsy specimens collected from stage II and III rectal adenocarcinoma patients before neoadjuvant treatment was performed and compared with residual tumor tissues removed by surgery after neoadjuvant therapy. Three proteins, Ku70, Ku80, and Rab5C, exhibited a significant increase in expression after chemoradiation. To better understand the role of these proteins in therapy resistance, a rectal adenocarcinoma cell line was irradiated to generate a radiotherapy-resistant lineage. These cells overexpressed the same three proteins identified in the tissue samples. Furthermore, radiotherapy resistance in this in vitro model was found to involve modulation of epidermal growth factor receptor (EGFR) internalization by Rab5C in response to irradiation, affecting expression of the DNA repair proteins, Ku70 and Ku80, and cell resistance. Taken together, these findings indicate that EGFR and Rab5C are potential targets for the sensitization of rectal cancer cells and they should be further investigated. KEY MESSAGES: • Rab5C orchestrates a mechanism of radioresistance in rectal adenocarcinoma cell. • Rab5C modulates EGFR internalization and its relocalization to the nucleus. • In the nucleus, EGFR can modulate the expression of the DNA repair proteins, Ku70 and Ku80. • Rab5C, Ku70, and Ku80 are overexpressed in tumor tissues that contain tumor cells that are resistant to chemoradiation treatment.

Locally advanced breast cancer: Tumor-infiltrating lymphocytes as a predictive factor of response to neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the pathologic response after neoadjuvant chemotherapy in patients with breast cancer according to the stromal tumor-infiltrating lymphocytes (TILs) as well as the evaluation of overall and disease-free survival according to TILs. METHODS: A six years (2008-2013) review was done including patients with locally advanced breast cancer that received neoadjuvant therapy and then surgery. An evaluation of the percentage of TILs was done in the pretreatment biopsies and a correlation analysis and survival curves were done. RESULTS: 187 patients were evaluated. The pathological complete response (pCR) in patients with TILs ≥30% was 58.5%, and in patients with TILs < 30% was 11% (p <0.001). An Odds Ratio of 8.85 was obtained in patients with TILs ≥30% to achieve a pCR. This relationship was seen in patients with HER2-enriched and triple-negative subtypes. No correlation between TILs and survival was obtained (OS: log-rank; p = 0.834; DFS: log-rank; p = 0.937). CONCLUSIONS: The study of TILs is important because they represent an additional tool to predict the response to neoadjuvant treatment mostly in HER2-enriched and triple-negative subtypes of breast cancer.

Neoadjuvant isolated limb perfusion in newly diagnosed untreated patients with locally advanced soft tissue sarcomas of the extremities: the Gustave Roussy experience.

BACKGROUND: Limb-sparing surgery in locally advanced soft tissue sarcomas (LA STS) is challenging. The aim of this study is to evaluate upfront isolated limb perfusion (ILP) in untreated patients with LA STS. METHODS: All consecutive patients with LA STS of the limbs deemed borderline or unresectable and treated with upfront ILP as induction treatment between 2003 and 2016 were included. Demographic, clinical and long-term characteristics were obtained and retrospectively analyzed. RESULTS: 41 patients (pts), with a median age of 51 years [range 21-76], were identified (lower limb 68%, upper limb 32%). Liposarcoma and undifferentiated pleomorphic sarcoma were the most common subtypes (27% and 22%, respectively). Acute toxicities, using Wieberdink classification, were grade II (35 pts, 85%), grade III (2 pts, 5%) and no grade IV-V. Local control rate was 98%. 32 pts had limb-sparing surgery (78%). 1 pt had an early amputation due to progressive disease after ILP. 8 pts were not operated (four had RT alone, one had distant metastases, two had a complete response and one died 3 months after ILP of a pulmonary embolism). 36 pts (84%) received postoperative RT. After a median follow-up of 43 months, 18 pts (47%) relapsed. Median disease-free survival (DFS) was 6.7 years. The median overall survival (OS) was not reached. The 1-year, 5-year and 10-year DFS and OS rates were, respectively, 75%, 50% and 45%, and 90%, 63% and 55%. CONCLUSION: Upfront ILP is an efficient and well-tolerated limb-sparing procedure in borderline or unresectable LA STS without hampering OS.

Efficacy of Anti-HER2 Agents in Combination With Adjuvant or Neoadjuvant Chemotherapy for Early and Locally Advanced HER2-Positive Breast Cancer Patients: A Network Meta-Analysis.

BACKGROUND: Several (neo)adjuvant treatments for patients with HER2-positive breast cancer have been compared in different randomized clinical trials. Since it is not feasible to conduct adequate pairwise comparative trials of all these therapeutic options, network meta-analysis offers an opportunity for more detailed inference for evidence-based therapy. METHODS: Phase II/III randomized clinical trials comparing two or more different (neo)adjuvant treatments for HER2-positive breast cancer patients were included. Relative treatment effects were pooled in two separate network meta-analyses for overall survival (OS) and disease-free survival (DFS). RESULTS: 17 clinical trials met our eligibility criteria. Two different networks of trials were created based on the availability of the outcomes: OS network (15 trials: 37,837 patients); and DFS network (17 trials: 40,992 patients). Two studies-the ExteNET and the NeoSphere trials-were included only in this DFS network because OS data have not yet been reported. The concept of the dual anti-HER2 blockade proved to be the best option in terms of OS and DFS. Chemotherapy (CT) plus trastuzumab (T) and lapatinib (L) and CT + T + Pertuzumab (P) are probably the best treatment options in terms of OS, with 62.47% and 22.06%, respectively. In the DFS network, CT + T + Neratinib (N) was the best treatment option with 50.55%, followed by CT + T + P (26.59%) and CT + T + L (20.62%). CONCLUSION: This network meta-analysis suggests that dual anti-HER2 blockade with trastuzumab plus either lapatinib or pertuzumab are probably the best treatment options in the (neo)adjuvant setting for HER2-positive breast cancer patients in terms of OS gain. Mature OS results are still expected for the Aphinity trial and for the sequential use of trastuzumab followed by neratinib, the treatment that showed the best performance in terms of DFS in our analysis.