Combining bi-modal imaging and immunohistochemical indicators to predict axillary lymph nodes status in cN 1 breast cancer patients receiving neoadjuvant chemotherapy / 中华超声影像学杂志

Objective:To investigate whether ultrasound features, mammographic features and immunohistochemical indicators show any association with rates of axillary pathologic complete response(pCR) in cN 1 breast cancer patients receiving neoadjuvant chemotherapy(NAC), and to construct prediction models of axillary pCR to predict axillary lymph nodes (ALN) status, so as to select suitable patients for less invasive axillary surgery after NAC. Methods:This retrospective study evaluated 134 consecutive cN 1 breast cancer patients with ALN metastasis who underwent NAC in the Second Affiliated Hospital and Tumor Hospital of Harbin Medical University from July 2020 to July 2022. According to the pathological results of ALN surgery after NAC, the cases were divided into pCR and non pathologic complete respose(npCR) groups. The ultrasound images, mammographic images and immunohistochemical indicators of the two groups were compared. In terms of logistic regression algorithm, the model A(the ultrasound model), the model B(the ultrasound combined with mammography model), the model C(the ultrasound combined with immunohistochemistry model) and the model D(the ultrasound combined with mammography and immunohistochemistry model) were respectively established for predicting the pathological state of axillary lymph nodes in breast cancer patients, ROC curves were plotted to evaluate the performance of the models, and the diagnostic efficiency of different models was compared by Delong′s test. The model with the best predictive performance was shown in a nomogram. Results:①The P values between two groups of the short diameter of ALN, the ratio of long/short diameter of ALN, fatty hilum and central hilar vascularity, mammographic spiculation, estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor receptor 2(HER2) were <0.05 by the t test and χ 2 test analysis. ②The ratio of long/short diameter and fatty hilum in the model A were independent factors for predicting the pathological status of ALN after NAC. The independent predictors of model B and Model C were respectively added with mammographic spiculation and immunohistochemical indicators (ER, PR) on the basis of model A. In the model D, the ratio of long/short diameter, short diameter, fatty hilum, mammographic spiculation, and immunohistochemical indicators (ER, PR) remained significant independent predictors associated with axillary pCR. ③The area under ROC curve (AUC) of the model A, B, C, D was 0.78, 0.84, 0.84 and 0.89, respectively. The sensitivity was 0.71, 0.80, 0.78 and 0.86, the specificity was 0.76, 0.74, 0.76 and 0.80, and the accuracy was 0.73, 0.76, 0.77 and 0.83, respectively. ④Delong′s test showed the model D had an improved AUC of 0.89(0.89 vs 0.78, 0.84, 0.84, all P<0.05). Conclusions:The prediction models combining bi-modal imaging and immunohistochemical indicators show good prediction ability and can provide reference for selecting suitable patients for less invasive axillary surgery after NAC.

Neoadjuvant strategy usher in a new era of quasi-individualized treatment for early breast cancer / 国际外科学杂志

Treatment sequencing in early-stage breast cancer has significantly changed in recent years. Instead of surgery-adjuvant chemotherapy mode, several clinical trials showed benefits using administering systemic chemotherapy (and human epidermal growth factor receptor 2 targeted therapies) prior to surgery. Neoadjuvant therapy (NAT) could frequently downstage the primary tumor and lymph nodes, allowing conversion of the planned surgery form inoperable to operable one, from a mastectomy to a lumpectomy, and potentially allowing omission of axillary lymph node dissection. These benefits also include providing the opportunity to monitor the individual drug response and more accurate prognostic estimates based on the extent of residual cancer that can guide additional adjuvant treatment. This allows escalation or de-escalation of NAT: patients who achieved pathologic complete response could be spared further chemotherapy or de-escalation of locoregional therapies, while those with residual cancer could receive additional systemic therapy postoperatively. NAT is not an option anymore but a platform for personalized breast cancer therapy.

Establishment of random forest model and its predictive value for pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy / 肿瘤研究与临床

Objective:To investigate the predictive value of established random forest model for pathologic complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy.Methods:The clinicopathologic data of 142 primary breast cancer patients undergoing breast-conserving surgery or modified radical mastectomy after neoadjuvant chemotherapy from Cangzhou Central Hospital between January 2010 and October 2021 were retrospectively analyzed. Histologically, breast and axillary lymph node without residual infiltrated tumors was treated as pCR. The patients were divided into pCR group (23 cases) and non-pCR group (119 cases) according to whether patients achieved pCR or not, and the differences of clinicopathologic data between the two groups were compared. The risk factors affecting pCR were identified by using logistic regression analysis, random forest model was established by using random forest function of R statistical software, and Gini index of random forest algorithmic was used to order the importance of variables. The receiver operating characteristic (ROC) curve was used to assess the value of random forest model in predicting the efficacy of neoadjuvant chemotherapy.Results:The overall pCR ratio after neoadjuvant chemotherapy was 16.20% (23/142). The proportion of tumor diameter ≤5 cm, negative axillary lymph node, negative human epidermal growth factor receptor 2 (HER2), Ki-67 positive index >20%, histological grade 2, and neoadjuvant chemotherapy regimens including targeted therapy in pCR group was higher than that in non-pCR group, and the difference was statistically significant (all P < 0.05). Univariate logistic regression analysis showed that tumor diameter, axillary lymph node, HER2, Ki-67, histological grade, and neoadjuvant chemotherapy regimens were related with pCR (all P < 0.05). Multivariate logistic regression analysis showed that tumor diameter >5 cm ( OR = 5.85, 95% CI 1.28-26.67, P = 0.022), positive axillary lymph node ( OR = 11.22, 95% CI 1.84-68.42, P = 0.009), positive HER2 ( OR = 7.35, 95% CI 1.45-37.26, P = 0.016), Ki-67 positive index ≤20% ( OR = 1.03, 95% CI 1.01-1.06, P = 0.017), histological grade 3 ( OR = 7.37, 95% CI 1.24-43.86, P = 0.028), and non-targeted therapy ( OR = 0.02, 95% CI 0.00-0.25, P = 0.003) were independent risk factors of pCR. Random forest algorithm showed that the importance order of risk factors of pCR was successively Ki-67 low expression, positive axillary lymph node, tumor diameter >5 cm, positive HER2, non-targeted therapy and histological grade 3. The area under the ROC curve of random forest model for predicting pCR was 0.84 (95% CI 0.74-0.93); the sensitivity was 87.0% and specificity was 72.3% when the optimal cut-off value was 0.88. Conclusions:Low expression of Ki-67, positive axillary lymph node, tumor diameter >5cm, positive HER2, non-targeted therapy and histological grade 3 are risk factors of pCR in breast cancer patients after neoadjuvant chemotheapy. Random forest model helps to predict pCR in breast cancer patients after neoadjuvant chemotheapy.

Construction of a nomogram prediction model for pathological complete response (pCR) of ipsilateral supraclavicular lymph node after neoadjuvant chemotherapy for breast cancer with first diagnosis of ipsilateral supraclavicular lymph node metastasis / 中华肿瘤杂志

Objective: To develop a predictive model for pathologic complete response (pCR) of ipsilateral supraclavicular lymph nodes (ISLN) after neoadjuvant chemotherapy for breast cancer and guide the local treatment. Methods: Two hundred and eleven consecutive breast cancer patients with first diagnosis of ipsilateral supraclavicular lymph node metastasis who underwent ipsilateral supraclavicular lymph node dissection and treated in the Breast Department of Henan Cancer Hospital from September 2012 to May 2019 were included. One hundred and forty two cases were divided into the training set while other 69 cases into the validation set. The factors affecting ipsilateral supraclavicular lymph node pCR (ispCR)of breast cancer after neoadjuvant chemotherapy were analyzed by univariate and multivariate logistic regression analyses, and a nomogram prediction model of ispCR was established. Internal and external validation evaluation of the nomogram prediction model were conducted by receiver operating characteristic (ROC) curve analysis and plotting calibration curves. Results: Univariate logistic regression analysis showed that Ki-67 index, number of axillary lymph node metastases, breast pCR, axillary pCR, and ISLN size after neoadjuvant chemotherapy were associated with ispCR of breast cancerafter neoadjuvant chemotherapy (P<0.05). Multivariate logistic regression analysis showed that the number of axillary lymph node metastases (OR=5.035, 95%CI: 1.722-14.721, P=0.003), breast pCR (OR=4.662, 95%CI: 1.456-14.922, P=0.010) and ISLN size after neoadjuvant chemotherapy (OR=4.231, 95%CI: 1.194-14.985, P=0.025) were independent predictors of ispCR of breast cancer after neoadjuvant chemotherapy. A nomogram prediction model of ispCR of breast cancer after neoadjuvant chemotherapy was constructed using five factors: number of axillary lymph node metastases, Ki-67 index, breast pCR, axillary pCR and size of ISLN after neoadjuvant chemotherapy. The areas under the ROC curve for the nomogram prediction model in the training and validation sets were 0.855 and 0.838, respectively, and the difference was not statistically significant (P=0.755). The 3-year disease-free survival rates of patients in the ispCR and non-ispCR groups after neoadjuvant chemotherapy were 64.3% and 54.8%, respectively, with statistically significant differences (P=0.024), the 3-year overall survival rates were 83.8% and 70.2%, respectively, without statistically significant difference (P=0.087). Conclusions: Disease free survival is significantly improved in breast cancer patients with ispCR after neoadjuvant chemotherapy. The constructed nomogram prediction model of ispCR of breast cancer patients after neoadjuvant chemotherapy is well fitted. Application of this prediction model can assist the development of local management strategies for the ipsilateral supraclavicular region after neoadjuvant chemotherapy and predict the long-term prognosis of breast cancer patients.

Cambios en el perfil inmunohistoquímico pre y post neoadyuvancia en cáncer de mama. Experiencia del Hospital Británico de Buenos Aires / Changes in biomarkers in pre and post neoadjuvant breast carcinoma

Introducción: actualmente la quimioterapia neoadyuvante ha ampliado sus indicaciones en el tratamiento del cáncer de mama. Se observó variabilidad en la expresión de biomarcadores postneoadyuvancia que pueden acompañarse de cambios en el tratamiento adyuvane. Objetivos: el objetivo principal fue evaluar la variabilidad de biomarcadores pre y post neoadyuvancia. Los objetivos secundarios fueron determinar qué subtipo inmunohistoquímico tumoral alcanzó más frecuentemente la respuesta patológica completa (PCR), si la variación en los biomarcadores derivó en un cambio de inmunofenotipo y posteriormente en una modificación del tratamiento adyuvante. Material y método: se realizó un estudio retrospectivo observacional de las pacientes con diagnóstico de cáncer de mama que realizaron neoadyuvancia en el servicio de mastología del Hospital Británico de Buenos Aires entre enero 2009 y junio 2019. Resultados: se incluyeron 127 pacientes. La variabilidad observada para receptores de estrógeno (RE) fue de 7,6%, resultando no estadísticamente significativo. Para receptores de progesterona (RP) fue de 28,3% y para HER2 fue de 13,1%, estos cambios fueron estadísticamente significativos. El inmunofenotipo tumoral que alcanzó más frecuentemente la PCR fue el grup RH-/HER2+. Hubo cambios en el inmunofenotipo tumoral en 17 casos y modificaciones al tratamiento adyuvante en 5 de estos. Conclusiones: en este estudio observamos una variabilidad estadísticamente significativa en la expresión de RP y HER2 posteriormente al tratamiento neoadyuvante. En cambio la variabilidad de RE no es estadísticamente significativa. Estos cambios determinan modificaciones en el inmunofenotipo tumoral y en el tratamiento adyuvante en el 29,4% de estos casos (5,4% del total de la serie), justificando la reevaluación de biomarcadores en la pieza quirúrgica. La tasa de PCR fue del 27,6%. Se observó con mayor frecuencia en el grupo RH-/HER2+ alcanzando un valor de 83,3%.

Introduction: nowadays neoadjuvant chemotherapy has extended its indications in breast cáncer treatment. A variantion in tumoral biomark expression has been observed after neoadjuvant treatment, this can be accompanied by a modification in adjuvant treatment. Objetives: to evaluate the variability in biomarkers before and after neoajuvant chemotherapy. To observe which inmunehistochemical subtype reache most frequently pathologic complete response, to determine if changes in biomarkers derived in a change in adjuvant treatment. Material and method: this is an observational retrospective study on patients with breast cáncer diagnosis who underwent neoadjuvant chemotherapy in Buenos Aires British Hospital between 2009 and june 2019. Results: the variability observed for estrogen receptor was 7,6%, not statistically significant; for progesterone receptor was 28,3%, for HER2 13,1%, these modifications were statistically significant. Pathologic complete response was achieved most frequently by RH-/HER2+ carcinomas. We observed changes in subtype in 17 cases ant modifications to adjuvant treatment in 5 cases. Conclusions: in this study we observed modifications in progesterone receptors and HER2 expression before and after neoadjuvant treatment, these were statistically significan. The modifications in estrogen receptors expression were not statistically significant. They led to changes in tumoral subtype and in the adjuvant treatment in 29,4% of the cases. This justifies retesting tumoral biomarkers after the neadjuvant setting. The rate of pathologic complete response was of 27,6%, mainly given by RH-/HER2 + tumors.

Predictive value of combination of MRI tumor regression grade and apparent diffusion coefficient for pathological complete remission after neoadjuvant treatment of locally advanced rectal cancer / 中华胃肠外科杂志

Objective: Pelvic high-resolution magnetic resonance imaging (MRI) has now become a standard method for evaluating the efficacy of neoadjuvant treatment for locally advanced rectal cancer (LARC). However, this traditional morphological qualitative assessment method based on T2-weighted imaging (T2WI) is not effective in predicting pathological complete remission (pCR). The purpose of this study is to investigate whether combining the magnetic resonance tumor regression grade (mrTRG) with apparent diffusion coefficient (ADC) can improve diagnostic value for pCR after preoperative neoadjuvant chemoradiotherapy (nCRT) of LARC. Methods: This was a diagnostic study. Clinicopathological data of 134 LARC patients who received nCRT and radical surgery in the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2019 were retrospectively analyzed. All the patients underwent MRI which included T2WI and DWI sequences before and 8 weeks after nCRT. Two radiologists independently drew ROIs on T2WI and DWI to estimate mrTRG stage and calculate the mean ADC value. Receiver operating characteristics (ROC) method was applied to evaluate the predict value of mrTRG combined with mean ADC value for pCR. Results: Of 134 LARC patients, 85 were male and 49 were female with median age of 58 (28-82) years. After nCRT, MRI suggested 21 patients (15.7%) had clinical complete remission (cCR), e.g. mrTRG stage 1-2. Postoperative pathology revealed 31 (23.1%) patients had pCR. The evaluations of mrTRG and ADC value by the two readers were highly consistent, and the intra-group correlation coefficients were 0.83 (95% CI: 0.703-0.881) and 0.96 (95% CI: 0.989-0.996), respectively. There was a negative correlation between mrTRG and pCR (r(s)=-0.505, P<0.01), and a positive correlation between mean ADC value and pCR (r(s)=0.693, P<0.01). The ROC curve showed that mrTRG alone had a medium predictive value for pCR, with an area under the curve (AUC) of 0.832 (95% CI: 0.743-0.921); the mean ADC value had a higher predictive value for pCR, with AUC of 0.906 (95% CI: 0.869-0.962). The predictive value of the combined model of mrTRG and ADC value for pCR was significantly better than that of mrTRG alone (P=0.015), and the AUC was 0.908 (95% CI: 0.849-0.968). Conclusion: Both mrTRG and mean ADC value can be non-invasive methods to predict the efficacy of nCRT for LARC. Combining the mean ADC value with mrTRG can result in better pCR prediction.

Cáncer de mama Triple Negativo / Triple Negative Breast Cancer

El cáncer de mama Triple Negativo ha sido estudiado a lo largo de los años principalmente por ser uno de los de peor pronóstico y, además, por carecer de terapia blanco. El debut de esta patología se puede dar de diversas formas, y es en función de esto que el especialista optará entre distintas medidas: ya sea instaurará tratamiento adyuvante o neoadyuvante o enfrentará directamente la enfermedad metastásica. Si bien muchas veces las terapias a utilizar no se encuentran bien establecidas, las drogas quimioterápicas no difieren de las de los otros subtipos. Pero, al ser tumores que se asocian con mayor frecuencia a mutaciones en el brca, se han investigado tratamientos que apuntan más hacia el defecto de reparación del adn mediante la recombinación homóloga, como son los platinos y los inhibidores del parp. Por otro lado, no se debe dejar de mencionar las terapias dirigidas hacia los distintos subtipos tumorales como, por ejemplo, los antagonistas androgénicos que aún se encuentran en estudio. Sabemos que el cáncer de mama Triple Negativo es una patología extremadamente difícil de tratar, pero todavía quedan en el tintero investigaciones para esclarecer y enfocar las terapias blanco según cada subtipo dentro de estos tumores

Over the years, Triple Negative breast cancers have been studied, mainly because of its poor prognosis but also because it lacks a target therapy. Its debut may occur in different ways, therefore specialists can choose between different measures for treatment. The choices lay between adjuvant or neoadjuvant therapies or to directly face metastatic disease. Although these therapies are not fully established, chemotherapeutic drugs do not differ from other breast cancer subtypes. The association between these tumors and brca mutations is so high, target treatments have been focusing in dna defect repair, through homologous recombination, such as platinum-based chemotherapy and parp inhibitors. Other target therapies should be taken into account, such as androgenic antagonists, which are still being studied. Considering the nature of such an heterogeneous disease, which is extremely difficult to treat, we should acknowledge research in this subject is yet to be clarified to be able to provide new target therapies for each subtype within the triple negative tumors

Respuesta patológica completa, cirugía conservadora y recidivas a distancia en tumores localmente avanzados: resultados en 30 años de tratamiento neoadyuvante / Complete Pathologic Response, Breast Conserving Surgery and Distant Recurrence in Locally Advanced Breast Cancer: Results within 30 years of Neoadjuvant Therapy

Introducción La quimioterapia neoadyuvante (qtn) es el tratamiento inicial para pacientes con tumores localmente avanzados, permitiendo la evaluación de la sensibilidad in vivo a los agentes antineoplásicos y la planificación de estrategias quirúrgicas con resultados cosméticos favorables. Objetivos Comparar la tasa de respuesta patológica completa (pcr), la tasa de conversión a cirugía conservadora (tccc), el tiempo a la recaída a distancia (trad) y la supervivencia libre de enfermedad a distancia (sled) a 60 meses en pacientes con cáncer de mama Estadio III que fueron tratadas con qtn antes y después del año 2007 Material y método Se trata de un estudio observacional de cohortes retrospectivo en el que se analizaron registros de pacientes con cáncer de mama Estadio III operadas entre 1987 y 2016 que hubieran realizado qtn . Se constituyeron dos cohortes: en la primera se reunieron pacientes tratadas entre 1987 y 2006; en la segunda se agruparon aquellas tratadas entre 2007 y 2016. Se estableció esta diferencia dado que a partir de 2007 hubo cambios en la modalidad terapéutica: se administró la quimioterapia en forma continua antes de la cirugía y se introdujeron los taxanos y la terapia anti-her2 neu en los esquemas de qtn . En total se registraron 202 pacientes, 146 pertenecientes a la primera cohorte y 56 pertenecientes a la segunda. La mediana de edad y el tamaño tumoral fueron similares entre ambos grupos, mientras que en el segundo grupo observamos mayor porcentaje de tumores Grado 3 y mayor carga tumoral axilar. Resultados La tasa de pcr fue del 2% (n=3) para el primer grupo y de 13% (n=7) para el segundo (p=0,0022). La tasa de conversión a cirugía conservadora fue del 27% (n=20) para el primer grupo y del 41% (n=17) para el segundo, observándose un 14% más de cirugías conservadoras en este último (p=0,11). La mediana de trad fue de 33 meses para el primer grupo y de 46,5 meses para el segundo (p=0,044). La sled a 60 meses fue del 58% vs el 74% para el primer y segundo grupo respectivamente (p=0,039). Conclusiones Los cambios en la modalidad terapéutica en qtn en nuestra práctica se tradujeron en mayores tasas de pcr, mayor porcentaje de conversión a cirugía conservadora, mayor tiempo a la recidiva a distancia y mayor supervivencia libre de enfermedad a distancia

Introduction Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer, allowing surgical planning with favorable cosmetic outcome and evaluation of in vivo response to antineoplastic agents. Objectives To compare pathologic complete response, breast conserving surgery conversion rates, time to distant relapse and distant recurrence free survival after 60 months in patients with Stage III breast cancer who received neoadjuvant chemotherapy before and after year 2007. Materials and method Observational retrospective cohort study analizing database and medical records of patients with Stage III breast cancer who had surgery after neoadjuvant therapy between 1987 and 2016. We divided the population into two cohorts, one with patients treated between 1987 and 2006, and another one with those ones treated between 2007 and 2016. We established that difference given that from 2007 and onwards there were major changes in treatment modality: chemotherapy was administered completely before surgery, and Taxane-containing regimens as well as Anti-her2 therapies were included. We registered 202 patients, 146 in the first group and 56 in the second. While median of age and tumor size were similar between groups, axillary tumor burden and histologic grade were higher in the second group. Results Pathologic complete response rate was 2% for the first group and 13% for the second (p=0.0022). Breast conserving surgery conversion rates were 27% vs 41%, with 14% more breast conserving surgeries in the second cohort. Median time to distant recurrence was 33 months vs 46.5 months (p=0.044) and distant recurrence free survival was 58% vs 74% (p=0.039) for groups 1 and two 2 respectively. Conclusions Changes in treatment modality in our practice resulted in better pcr outcomes, more breast conserving surgery conversion rates, longer time to distant relapse and a better distant recurrence free survival

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.

Oncologic Outcomes in Patients Who Undergo Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision for Locally Advanced Rectal Cancer: A 14-Year Experience in a Single Institution

PURPOSE: This study evaluated the oncologic outcomes of locally advanced rectal cancer patients who underwent preoperative neoadjuvant chemoradiotherapy (CRT) followed by surgery and determined the prognostic significance of pathologic complete response (pCR). METHODS: Between January 2002 and December 2015, 580 patients with rectal cancer who underwent surgery after neoadjuvant CRT were identified. Survival according to tumor response to CRT and pathologic stage was analyzed using the Kaplan-Meier method, and the Cox proportional hazard model was used to identify factors associated with survival outcomes. RESULTS: A total of 111 patients (23.7%) achieved pCR while the other 469 patients showed residual disease. Patients with pCR had a lower pretreatment carcinoembryonic antigen level and earlier cT classification than those with residual disease. With a median follow-up of 78 months, disease-free survival (DFS) and overall survival (OS) were significantly better in the pCR group than in the residual disease group. The 5-year DFS and 5-year OS for patients with ypStage 0, I, II, or III were 92.5%, 85.1%, 72.2%, 54.3% (P < 0.001) and 94.5%, 91.0%, 83.1%, 69.3%, respectively (P < 0.001). Pathologic AJCC stage after CRT was the most statistically significant independent predictor of OS (HR, 6.97 [95% confidence interval, 3.16–15.39] for stage III vs. stage 0) and DFS (HR, 7.30 [95% confidence interval, 3.63–14.67] for stage III vs. stage 0). CONCLUSION: Rectal cancer patients who achieved pCR showed improved survival compared to those with residual disease after preoperative CRT. Moreover, pCR was an independent indicator of OS and DFS, and pathologic AJCC stage was correlated with survival after preoperative CRT.

How to Achieve a Higher Pathologic Complete Response in Patients With Locally Advanced Rectal Cancer Who Receive Preoperative Chemoradiation Therapy

The current standard of care for treating patients with locally advanced rectal cancer includes preoperative chemoradiation therapy (PCRT) followed by a total mesorectal excision and postoperative adjuvant chemotherapy. A subset of these patients has achieved a pathologic complete response (pCR) and they have shown improved disease-free and overall survival compared to non-pCR patients. Thus, many efforts have been made to achieve a higher pCR through PCRT. In this review, results from various ongoing and recently completed clinical trials that are being or have been conducted with an aim to improve tumor response by modifying therapy will be discussed.

Clinical verification of sensitivity to neoadjuvant chemoradiotherapy in cases of locally advanced rectal cancer / 中国实用外科杂志

OBJECTIVE: To identify the influencing factors of pathologic complete response(pCR) after neoadjuvant chemoradiotherapy(nCRT) for rectal cancer.METHODS: The clinical data of 185 locally advanced rectal cancer patients admitted at the Sixth Affiliated Hospital Sun Yat-sen University between January 2013 and October 2016 were analyzed retrospectively. Patients were divided into two groups according to their responses to neoadjuvant therapy: the pCR(49 patients)and non-pCR groups(136 patients). The correlation between clinicopathological factors and PCR was analyzed.RESULTS:The rate of pathologic complete response(pCR) was 26.5%,and downstaging rate(ypStage 0 to 1)was achieved 55.8%. In univariate analyses,carcinoembryonic antigen concentration(P=0.039),clinical stage T(P=0.004),stage N(P=0.032)and neoadjuvant chemoradiotherapy with oxaliplatin(P=0.003)were significantly associated with pCR. In multivariate analysis,clinical stage T2 and neoadjuvant chemoradiotherapy with oxaliplatin were significantly associated with pCR,while CEA level was a marginally significant risk factor.CONCLUSION: Stage T2 cancer and fluorouracil-based neoadjuvant chemoradiotherapy with oxaliplatin are independent clinical predictors for achieving pCR.

The association between the expression and activity of indoleamine 2,3-dioxygenase and the efficacy of neoadjuvant chemotherapy in patients with breast cancer / 中国肿瘤临床

Objective:To investigate the association between indoleamine 2,3-dioxygenase(IDO)expression in tumor tissue,its periph-eral blood activity, and the efficacy of neoadjuvant chemotherapyin patients with breast cancer. Methods: Immunohistochemistry (IHC)and high-performance liquid chromatography(HPLC)were used to measure IDO protein expression in tumor tissue,and kynuren-ine(Kyn),tryptophan(Trp),and IDO activity(Kyn/Trp)in peripheral blood before neoadjuvant chemotherapy in 53 patients with breast cancer from Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2016.The correlations between the expression and activity of IDO and the efficacy of chemotherapy were analyzed.Results:In tumor tissue,IDO expression-before neoadjuvant chemotherapy was related to clinical tumor stages(P=0.006),node stages(P=0.020),clinical stages(P=0.045),and estrogen receptor(ER)status(P=0.014).High IDO activity before neoadjuvant chemotherapy in peripheral blood was associated with high IDO expression in tumor tissue(P=0.004),and was also correlated with clinical tumor stages(P=0.019)and node stages(P=0.047). Univariate analysis showed that the clinical efficacy of neoadjuvant chemotherapy was associated with pre-chemotherapeutic clinical tumor stages(P=0.049),ER status(P=0.025),and molecular subtype(P=0.014),while pathologic complete response(pCR)was related to pre-chemotherapeutic clinical tumor stages(P=0.014).Importantly,the clinical efficacy of neoadjuvant chemotherapy and pCR were both related to IDO expression and activity before chemotherapy(all P<0.05).Multivariate analysis showed that pre-chemotherapeu-tic IDO activity in peripheral blood was the only independent factor that affected pCR(P=0.032).Conclusions:Tumor tissue IDO expres-sion and peripheral blood IDO activity before chemotherapy were associated with chemotherapy efficacy,and could provide promising information for the clinical prediction of chemotherapy sensitivity.

Prospective phase Ⅱ study of neoadjuvant chemoradiotherapy followed by chemotherapy in locally advanced rectal cancer / 中华放射医学与防护杂志

Objective To evaluate the efficacy and safety of adding neoadjuvant chemotherapy following neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.Methods A total of 80 patients confirmed with locally advanced rectal cancer were enrolled during January 2012 and December 2015 in Guizhou Medical University Affiliated Cancer Hospital and were randomized with the method of lottery into the experimental group and the control group.In the experimental group,40 patients received 4 cycles of FOLFOX4 after chemoradiotherapy and then had total mesorectal excision (TME).Another 4 cycles of FOLFOX4 were administered after surgery.In the control group,40 patients had TME surgery 6-8 weeks after chemoradiotherapy and received 8 cycles of FOLFOX4 as adjuvant chemotherapy.Pelvic radiotherapy dose was 50 Gy in 25 fractions,5 days per week for 5 weeks.5-Fu continuous infusion was administered throughout radiotherapy.The pCR rate,downstaging rate,R0 resection rate,local recurrence rate,distant metastasis rate,survival rate,incidence of toxicities,surgical complications and completion of treatment were observed.Results The pCR rate was 20.0％ in the experimental group and 5.0％ in the control group (x2 =4.114,P ＜ 0.05).The downstaging rate was 77.4％ in the experimental group and 55.6％ in the control group(P ＞ 0.05).No statistically significant difference was observed in R0 resection rate,3-year local recurrence rate,3-year distant metastasis rate and 3-year survival rate between the two groups (P ＞ 0.05).Patients in the experimental group had higher completion rate of 8 cycles of systemic chemotherapy (87.1％ vs.61.5％,x2 =4.985,P ＜0.05).No statistically significant difference was observed in acute toxicities and postoperative complications.Conclusions Adding systemic chemotherapy after neoadjuvant chemoradiotherapy for locally advanced rectal cancer has significantly higher pCR rate and lower toxicities and side events compared with chemoradiotherapy alone.Longer follow-up and larger scale of clinical research are needed.Trial registration Chinese clinical trial registry,ChiCTR-IPR-17010454.

Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors

The purpose of this study was to retrospectively review the pathologic complete response (pCR) rate from patients (n=86) with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012). Stage II patients achieved a higher response rate compared to stage III (P=0.03). The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively) and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively). Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03) and death (HR=0.21; P=0.02). In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment.

Evaluation of Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Experience in a Single Institution over a 10-Year Period

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with favorable clinical outcome in breast cancer patients. However, the possibility that the prognostic significance of pCR differs among various definitions has not been established. METHODS: We retrospectively evaluated the pathologic response after NAC in 353 breast cancer patients and compared the prognoses after applying the following different definitions of pCR: ypT0/is, ypT0, ypT0/is ypN0, and ypT0 ypN0. RESULTS: pCR was significantly associated with improved distant disease-free survival (DDFS) regardless of the definition (ypT0/is, p = .002; ypT0, p = .008; ypT0/is ypN0, p < .001; ypT0 ypN0, p = .003). Presence of tumor deposits of any size in the lymph nodes (LNs; ypN ≥ 0(i+)) was associated with worse DDFS (ypT0 ypN0 vs ypT0 ypN ≥ 0(i+), p = .036 and ypT0/is ypN0 vs ypT0/is ypN ≥ 0(i+), p = .015), and presence of isolated tumor cells was associated with decreased overall survival (OS; ypT0/is ypN0 vs ypT0/is ypN0(i+), p = .013). Residual ductal carcinoma in situ regardless of LN status showed no significant difference in DDFS or OS (DDFS: ypT0 vs ypTis, p = .373 and ypT0 ypN0 vs ypTis ypN0, p = .462; OS: ypT0 vs ypTis, p = .441 and ypT0 ypN0 vs ypTis ypN0, p = .758). In subsequent analysis using ypT0/is ypN0, pCR was associated with improved DDFS and OS in triple-negative tumors (p < .001 and p = .003, respectively). CONCLUSIONS: Based on our study results, the prognosis and rate of pCR differ according to the definition of pCR and ypT0/is ypN0 might be considered a more preferable definition of pCR.

Effect of molecular subtype on chemosensitivity and survival in patients with breast cancer following neoadjuvant chemotherapy / 国际外科学杂志

Objective Pathologic complete response (pCR) has been suggested as a surrogate prognostic indicator in breast cancer patients treated with neoadjuvant chemotherapy.We assessed whether the likelihood of pCR and survival is associated with the immunohistochemistry-based molecular subtypes.Methods We retrospectively analyzed the records of l01 patients with breast cancer who received neoadjuvant chemotherapy between January 2007 and January 2010.Patients were dassified into four molecular subtypes based on the immunohistochemistry prnfiles of estrogen receptor,progesterone receptor,and HER2.Logistic regression was used to analyze variables associated with pCR.Results The pCR was achieved in 19 patients (18.8％).The triple negative subtype was an independent predictive factor for pCR (odds ratio,3.35,95％ confidence interval,1.25-9.79,P =0.012),and the Her-2 subtype showed a trend for higher pCR rates (odds ratio,3.11;95％ confidence interval,1.09-10.89,P =0.021) compared with the luminal A subtype.The pCR was significantly associated with prolonged disease-free survival (P =0.002).The triple negative subgroup had shorter disease-free survival (P =0.0006) and overall survival (P =0.008) than the other subgroups.Conclusions We demonstrated that the triple negative and Her-2 subtypes are more likely to obtain pCR when neoadjuvant chemotherapy is given,compared to the luminal A subtype.Despite the high pCR rate,the triple negative subtype showed worse survival outcomes,paradoxically,primarily due to patients who had residual disease.

A prognostic analysis of patients with pathologic complete response after preoperative neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 中华放射肿瘤学杂志

Objective To analyze the clinical factors for pathologic complete response ( pCR) after preoperative neoadjuvant chemoradiotherapy ( neo?CRT) for locally advanced rectal cancer. Methods From 2005 to 2012, 297 patients with locally advanced rectal cancer and complete clinical data were enrolled as subjects. Those patients were diagnosed with biopsy and treated with neo?CRT ( radiotherapy by 3?dimonsional conformal radiotherapy or volumetric?modulated arc therapy) followed by radical surgery. The logistic regression model was used for the multivariate analyses of the correlation of pCR with age, gender, distance between tumor and the anal verge, serum level of carcinoembryonic antigen ( CEA ) before treatment, hemoglobin level before treatment, cT staging, and cN staging. Results In all patients, 78 ( 26?7%) patients had pCR after treatment. The numbers of patients with pCR were 42( 34?4%) in patients with stage T1?T3 disease and 37(21?1%) in patients with stage T4 disease. In the patients with serum CEA levels no higher than 5?33 ng/ml, 55(36?4%) had pCR after treatment, while in the patients with serum CEA levels higher than 5?33 ng/ml, only 24( 16?4%) had pCR. The univariate analysis revealed that age, gender, distance between tumor and the anal verge, anemia before treatment, or cN staging were not related to pCR. The multivariate analysis showed that stage cT1?T3 and a serum CEA level no higher than 5?33 ng/ml before treatment were influencing factors for pCR after neo?CRT for locally advanced rectal cancer ( P=0?031,P=0?000) . Conclusions The clinical staging and the serum CEA level before treatment are influencing factors for pCR after neo?CRT for locally advanced rectal cancer. The serum CEA level before treatment can be considered as a predictor of pCR after neo?CRT for locally advanced rectal cancer.

Sustaining Blood Lymphocyte Count during Preoperative Chemoradiotherapy as a Predictive Marker for Pathologic Complete Response in Locally Advanced Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The objective of this study was to explore the relationship between the circulating lymphocyte level during preoperative chemoradiotherapy (CRT) and pathologic complete response (pCR) in locally advanced rectal cancer. MATERIALS AND METHODS: From May 2010 to May 2013, 52 patients treated with preoperative CRT followed by surgery, were analysed. Patients received conventional fractionated radiotherapy (50-54 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. Absolute blood lymphocyte counts and their relative percentage in total white blood cell counts were obtained from complete blood count tests performed prior to and after 4, 8, and 12 weeks of CRT. We analysed the association between achieving pCR and change in blood lymphocyte level during CRT, as well as clinical parameters. RESULTS: Among 52 patients, 14 (26.9%) had evidence of pCR. Sustaining the blood lymphocyte count during CRT (lymphocyte count at 4 weeks/baseline lymphocyte count > 0.35; odds ratio, 8.33; p=0.02) and initial carcinoembryonic antigen < 4.4 ng/mL (odds ratio, 6.71; p=0.03) were significantly associated with pCR in multivariate analyses. CONCLUSION: Sustaining blood lymphocyte count during preoperative CRT was predictive for pCR in rectal cancer. Further studies are warranted to investigate the association between pathologic responses and circulating lymphocyte count with its subpopulation during preoperative CRT.

Clinical efficacy of neoadjuvant chemoradiotherapy followed by surgery for locally advanced esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective To explore the efficacy of neoadjuvant chemoradiotherapy (CRT) followed by surgery for locally advanced esophageal squamous cell carcinoma (ESCC),and to investigate the correlation between a clinical complete response (cCR) and a pathologic complete response (pCR).Methods One hundred and fifty-eight patients with locally advanced thoracic ESCC from 2001 to 2013 were retrospectively analyzed.All patients received concurrent chemoradiotherapy followed by surgery.Platinumbased chemotherapy regimens were adopted in chemotherapy and a prescribed dose of 40 Gy in 20 fractions,5 fractions per week,was used in radiotherapy.The overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method,and pairwise comparisons and univariate prognostic analyses were performed using the log-rank test.Multivariable prognostic analyses were performed using the Cox regression model.Results The pCR rate was 41.1％ in all patients.After the treatment with neoadjuvant CRT,32(72.7％) out of 44 patients with a cCR had a pCR,but only 33(28.9％) out of 114 patients with a non-cCR had a pCR (P =0.000).The sensitivity,specificity,positive predictive value,and negative predictive value of a cCR in predicting a pCR were 49.2％,87.1％,72.7％,and 71.1％,respectively.The 3-year sample size was 91.The 3-year OS and DFS rates in all patients were 53.9％ and 48.6％,respectively.Patients with a cCR had significantly higher 3-year OS and DFS rates than those with a non-cCR (P =0.012;P =0.026),while patients with a pCR had significantly higher 3-year OS and DFS rates than those with a non-pCR (P =0.000;P =0.000).The multivariate analyses demonstrated that the pathologic response after CRT and chemotherapy regimen were the influencing factors for OS.The most common grade ≥3 acute adverse reaction was leucopenia (34.2％).Conclusions With a high pCR rate and tolerable adverse reactions,neoadjuvant CRT followed by surgery is a safe and effective option for locally advanced ESCC.The cCR rate after CRT is closely correlated with the pCR and OS rates.