Pathological Complete Response Group Research Articles

Pathologic complete response following neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma: Impact on survival and recurrence

BackgroundPathologic complete response after neoadjuvant treatment in pancreatic ductal adenocarcinoma is a rare occurrence. Similar to other malignancies, achieving a pathologic complete response in pancreatic ductal adenocarcinoma seems to correlate with improved survival. However, because of the rarity of such events, the true significance of pathologic complete response in pancreatic cancer remains unclear. The aim of the present study was to investigate the impact of pathologic complete response on survival and recurrence. MethodsIn a single-center retrospective study, pathologic complete response was defined as no evidence of viable tumor cells in resected specimen entirely sampled according to a rigorous protocol and in which a residual tumor bed was identified. Disease-specific survival and disease-free survival were measured from surgery. Independent predictors for disease-specific survival and disease-free survival were examined. ResultsOverall, 403 patients were included. Pathologic complete response was found in 15 patients (3.8%), after chemotherapy alone. After a median follow-up of 42 months (95% CI 38–45), 3-year disease-specific survival was 87% in pathologic complete response patients vs 43% in those without pathologic complete response (P = .014). The recurrence rate was 40% (n = 6/15) in the pathologic complete response group compared with 69.8% (n = 271/388) in those without pathologic complete response. Disease-free survival was longer in the pathologic complete response group, with higher 1- and 3-year rates compared with the no–pathologic complete response group (80% vs 60% and 48% vs 24%, respectively). Pathologic complete response was found to be an independent protective factor for disease-specific survival (P = .035) but not for disease-free survival (P = .052). ConclusionPathologic complete response in pancreatic ductal adenocarcinoma is not synonymous of cure but ensure a prolonged survival. Nevertheless, recurrence remains a significant concern, with high rates observed even among these exceptional responders.

Tumor Microenvironment Can Predict Chemotherapy Response of Patients with Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.

Triple-negative breast cancer (TNBC) is a breast cancer subtype that has poor prognosis and exhibits a unique tumor microenvironment. Analysis of the tumor microbiome has indicated a relationship between the tumor microenvironment and treatment response. Therefore, we attempted to reveal the role of the tumor microbiome in patients with TNBC receiving neoadjuvant chemotherapy. We collected TNBC patient RNA-sequencing samples from the Gene Expression Omnibus and extracted microbiome count data. Differential and relative abundance were estimated with linear discriminant analysis effect size. We calculated the immune cell fraction with CIBERSORTx and conducted survival analysis using the Cancer Genome Atlas patient data. Correlations between the microbiome and immune cell compositions were analyzed and a prediction model was constructed to estimate drug response. Among the pathological complete response group (pCR), the beta diversity varied considerably; consequently, 20 genera and 24 species were observed to express a significant differential and relative abundance. Pandoraea pulmonicola and Brucella melitensis were found to be important features in determining drug response. In correlation analysis, Geosporobacter ferrireducens, Streptococcus sanguinis, and resting natural killer cells were the most correlated factors in the pCR, whereas Nitrosospira briensis, Plantactinospora sp. BC1, and regulatory T cells were key features in the residual disease group. Our study demonstrated that the microbiome analysis of tumor tissue can predict chemotherapy response of patients with TNBC. Further, the immunological tumor microenvironment may be impacted by the tumor microbiome, thereby affecting the corresponding survival and treatment response.

Complete pathological response following neoadjuvant chemoradiotherapy in locally advanced colorectal carcinoma

Background: The prognosis of rectal cancer has improved with neoadjuvant treatment for locally advanced disease. Twenty percent of patients respond to treatment with complete pathological regression, which is clinically estimated with magnetic resonance imaging. Aim: describe the properties of the pathological complete response group of patients at our institution Materials and methods: All selected patients received LCCRT at the University Hospital for Tumors Sestre milosrdnice University Hospital Center, Zagreb, between January 2014 and December 2019 and were later surgically treated at the same facility. Results: We identified 23 patients with complete pathological responses, of which, despite surgery, seven progressed. We recorded a higher proportion of female patients in that group and younger age of onset. MRI preoperatively was not yet predictive of a complete pathological response. Conclusion: The proportion of patients with a complete pathological response is 16% in this cohort. All patients underwent surgery but did not receive consolidating therapy. About 30% progressed during the observed period.

Quantitative synthetic MRI for predicting locally advanced rectal cancer response to neoadjuvant chemoradiotherapy.

To investigate the value of pre-treatment quantitative synthetic MRI (SyMRI) for predicting a good response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. This prospective study enrolled 63 patients with locally advanced rectal cancer scheduled to undergo preoperative chemoradiotherapy from January 2019 to June 2021. T1 relaxation time (T1), T2 relaxation time (T2), proton density (PD) from synthetic MRI, and apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) were measured. Independent-sample t-test, the Mann-Whitney U test, the Delong test, and receiver operating characteristic curve (ROC) analyses were used to predict the pathologic complete response (pCR) and T-downstaging. Among the 63 patients, 19 (30%) achieved pCR and 44 (70%) did not, and 24 (38%) achieved T-downstaging, while 44 (62%) did not. The mean T1 and T2 values were significantly lower in the pCR group compared with those in the non-pCR group and in the T-downstage group compared with those in the non-T-downstage group (all p < 0.05). There were no significant differences in the PD and ADC values between the two groups. There were no significant differences between the mean values of T1 and T2 for predicting pCR after CRT (AUC, 0.767 vs. 0.831, p = 0.37). There were no significant differences between the AUC values of T1 and T2 values for the assessment of post-CRT T-downstaging (AUC, 0.746 vs. 0.820, p = 0.506). In patients with locally advanced rectal cancer, the synthetic MRI-derived T1 relaxation time and T2 relaxation time values are promising imaging markers for predicting a good response to neoadjuvant chemoradiotherapy. • Mean T1 and T2 values were significantly lower in the pathologic complete response group and the T-downstage group. • There were no significant differences in the proton density and apparent diffusion coefficient values between the two groups.

Surgical margin status and survival outcomes of breast cancer patients treated with breast-conserving surgery and whole-breast irradiation after neoadjuvant chemotherapy

The definition of "no tumor on ink" is generally applied for clear resection margin (RM) after breast-conserving surgery (BCS). However, few studies reported the effect of RM in the setting of neoadjuvant chemotherapy (NAC). We investigated the association between RM status and survival outcomes for those who underwent BCS after NAC for breast cancer. We retrospectively reviewed the data of 2,803 patients who underwent BCS and whole-breast irradiation after NAC between January 2008 and December 2016 from three institutions in South Korea. The 786 patients in the pathologic complete response group (RpCR) had significantly longer local recurrence-free survival (LRFS) than the 1,949 patients in clear or close RM and non-pCR group (R0) and the 68 patients in involved RM and non-pCR group (R1) (vs. R0, p = 0.001; vs. R1, p = 0.049). Patients in R0 showed no benefit in LRFS compared to R1 on both log-rank test (HR = 1.20; 95% C.I., 0.49-2.93; p = 0.692) and Cox regression analysis (HR = 2.05; 95% C.I., 0.64-6.58; p = 0.227). Subgroup analysis according to tumor subtypes revealed that there was no significant difference in LRFS, distant metastasis-free survival, and recurrence-free survival between the R0 and R1 group. Additionally, among 286 patients with pCR with residual ductal carcinoma in situ (DCIS) alone, RM status was not significantly associated with LRFS. Clear RM of specimen does not have benefit on LRFS after NAC. Additionally, for the patients showing pCR with residual DCIS in the breast, margin involvement also did not affect the risk of local recurrence.

Abstract 812: High RAD51 gene expression is associated with aggressive biology and with poor survival in breast cancer

Abstract INTRODUCTION: Homologous recombination deficiency (HRD) is involved in breast cancer carcinogenesis, however, activation of DNA repair in cancer cells may promote its survival and progression. RAD51 plays an essential role in homologous recombination with BRCA2. Recently, RAD51 has been highlighted to play a role in resistance to DNA-damaging chemotherapy or PARP inhibitors. We hypothesized that RAD51 as a prognostic and predictive biomarker of drug sensitivity in breast cancer. MATERIALS AND METHODS: Total of 4500 primary breast cancer patients from three independent cohorts were examined. High and low expression of RAD51 were divided by median RNA expression. Response to treatments were assessed in total of 3000 patients across 11 independent cohorts of breast cancer patients that received neoadjuvant chemotherapy. RESULTS: RAD51 was upregulated in cancer compared to normal tissues in the TCGA cohort and was positively correlated with HRD. Cancer with high RAD51 group enriched DNA repair gene set in gene set enrichment analysis (GSEA) in all cohorts and had high expression of HRD-related genes including BRCA1 and BRCA2. Histological grade and Ki67 expression were positively correlated with RAD51, and all cancer proliferation gene sets from Hallmark (E2F target, G2M checkpoint, Myc Targets v1 and v2, and Mitotic Spindle) were strongly enriched in the high RAD51 expression breast cancer in all cohorts. In TCGA, tumor mutation burden and neoantigen were also higher in tumor with high RAD51 expression, but RAD51 expression was not elevated in BRCA1 or BRCA2 mutant tumors. Cytolytic activity score, a marker of cancer immunity, was elevated high RAD51 group in two cohorts, and the immune cell fraction calculated by the xCell algorithm showed increase in immune cell infiltration, including CD4 memory T cells, Th1 cells, M1 macrophages and activated dendritic cells, in all cohorts, suggesting a certain level of activation of cancer immunity in this RAD51 high breast cancer group. However, contrary to previous reports, RAD51 expression in breast cancer cell lines did not show any association between sensitivity to chemotherapy or PARP inhibitors. Neither for the breast cancer NAC cohort, RAD51 expression was not increased in the residual burden group, but conversely increase in RAD51expression was observed in pathological complete response group in some cohorts. Surprisingly, RAD51 was significantly associated with worse overall survival in all three large cohorts included in this analysis, and with worse disease-specific survival in two cohorts. CONCLUSIONS: RAD51 expression was significantly associated with worse survival, but did not with treatment-responsive, suggesting its usefulness as prognostic, but not predictive, biomarker. Citation Format: Rongrong Wu, Ankit Patel, Yoshihisa Tokumaru, Mariko Asaoka, Masanori Oshi, Li Yan, Takashi Ishikawa, Kazuaki Takabe. High RAD51 gene expression is associated with aggressive biology and with poor survival in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 812.

Predictive Value of Multiparametric MRI for Response to Single-Cycle Induction Chemo-Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

ObjectivesTo assess the predictive value of multiparametric MRI for treatment response evaluation of induction chemo-immunotherapy in locally advanced head and neck squamous cell carcinoma.MethodsTwenty-two patients with locally advanced, histologically confirmed head and neck squamous cell carcinoma who were enrolled in the prospective multicenter phase II CheckRad-CD8 trial were included in the current analysis. In this unplanned secondary single-center analysis, all patients who received contrast-enhanced MRI at baseline and in week 4 after single-cycle induction therapy with cisplatin/docetaxel combined with the immune checkpoint inhibitors tremelimumab and durvalumab were included. In week 4, endoscopy with representative re-biopsy was performed to assess tumor response. All lesions were segmented in the baseline and restaging multiparametric MRI, including the primary tumor and lymph node metastases. The volume of interest of the respective lesions was volumetrically measured, and time-resolved mean intensities of the golden-angle radial sparse parallel-volume-interpolated gradient-echo perfusion (GRASP-VIBE) sequence were extracted. Additional quantitative parameters including the T1 ratio, short-TI inversion recovery ratio, apparent diffusion coefficient, and dynamic contrast-enhanced (DCE) values were measured. A model based on parallel random forests incorporating the MRI parameters from the baseline MRI was used to predict tumor response to therapy. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic performance.ResultsFifteen patients (68.2%) showed pathologic complete response in the re-biopsy, while seven patients had a residual tumor (31.8%). In all patients, the MRI-based primary tumor volume was significantly lower after treatment. The baseline DCE parameters of time to peak and wash-out were significantly different between the pathologic complete response group and the residual tumor group (p < 0.05). The developed model, based on parallel random forests and DCE parameters, was able to predict therapy response with a sensitivity of 78.7% (95% CI 71.24–84.93) and a specificity of 78.6% (95% CI 67.13–87.48). The model had an area under the ROC curve of 0.866 (95% CI 0.819–0.914).ConclusionsDCE parameters indicated treatment response at follow-up, and a random forest machine learning algorithm based on DCE parameters was able to predict treatment response to induction chemo-immunotherapy.

Evaluation of prognosis of rectal cancer patients with neoadjuvant chemoradiotherapy by clinical TNM stage: Is it suitable?

e16029 Background: In the Union for International Cancer Control /American Joint Committee on Cancer TNM classification system, the prognosis of rectal cancer patients with adjuvant treatment are based on pre-radiotherapy clinical TNM stage. However, the value of this classification system is still debated. Here, we find that neoadjuvant pathologic TNM stage may be better than clinical TNM stage in patients with rectal cancer. Furthermore, we propose a novel risk stratification which may be more accurate in the assessment of prognosis of these patients. Methods: Between 2010 and 2015, 316 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy followed by radical surgery were included for analysis. The clinicopathological factors for developing recurrences that affected prognosis were analyzed. Results: Our findings showed that the pathological complete response group had significantly better overall survival and recurrence-free survival than did the non-pCR group. Clinical N stage was not only an independent factor for developing recurrences but was also a significant prognostic factor in the pCR group, just as neoadjuvant pathologic TNM stage in the non-pCR group. Based on the independent prognostic factors, pCR patients were stratified into two recurrence risk categories: pCR with cN0 stage or pCR with cN+ stage. Non-pCR patients were stratified into three recurrence risk categories: non-pCR with ypTNM I stage, ypTNM II stage or ypTNM III stage, which might offer greater potential for the prognosis of patients with rectal cancer. Conclusions: Neoadjuvant pathologic TNM stage, rather than pre-radiotherapy clinical TNM stage, was an independent factor for developing recurrences in the non-pCR group. Furthermore, a novel risk stratification, which may be more accurate in the assessment of prognosis of rectal cancer patients, was proposed.

Predictive factors for tumour response after the neoadjuvant-treatment of rectal adenocarcinoma

PurposeStandard 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 methodsBetween 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 50.4Gy 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). ResultsMedian 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 TRG2‒3. Upper rectal tumours were identified to predictive factors for pathologic complete response by univariate analysis (p=0.002). TRG1‒3 was associated with intervals from chemo-radiation to surgery (p=0.004); TRG1‒3 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 5years 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). ConclusionsTumour 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 TRG1‒3. The relapse-free survival in pathologic complete response group was higher compared with non-pathologic complete response.

A Qualitative Transcriptional Signature for Predicting Recurrence Risk for High-Grade Serous Ovarian Cancer Patients Treated With Platinum-Taxane Adjuvant Chemotherapy.

Resistance to platinum and taxane adjuvant chemotherapy (ACT) is the main cause of the recurrence and poor prognosis of high-grade serous ovarian cancer (HGS-OvCa) patients receiving platinum-taxane ACT after surgery. However, currently reported quantitative transcriptional signatures, which are commonly based on risk scores summarized from gene expression, are unsuitable for clinical application because of their high sensitivity to experimental batch effects and quality uncertainties of clinical samples. Using 226 samples of HGS-OvCa patients receiving platinum-taxane ACT in TCGA, we developed a qualitative transcriptional signature, consisting of four gene pairs whose within-samples relative expression orderings could robustly predict patient recurrence-free survival (RFS). In two independent test datasets, the predicted non-responders had significantly shorter RFS than the predicted responders (log-rank p < 0.05). In a test dataset containing data for patient pathological response state, the signature reclassified 12 out of 22 pathological complete response patients as non-responders and two out of 16 pathological non-complete response patients as responders. Notably, the 12 predicted non-responders in the pathological complete response group had significantly shorter RFS than the predicted responders (log-rank p = 0.0122). This qualitative transcriptional signature, which is insensitive to experimental batch effects and quality uncertainties of clinical samples, can individually identify HGS-OvCa patients who are more likely to benefit from platinum-taxane adjuvant chemotherapy.

Pathological response and serum VEGF changes during chemoradiotherapy for esophageal carcinoma.

The aim of this study was to observe pathological response and change in serum vascular endothelial growth factor (VEGF) in esophageal carcinoma (EC) during chemoradiotherapy (CRT).Eighty-nine patients diagnosed with EC were treated with radiotherapy at the Department of Radiotherapy of the Second People's Hospital of Changzhou between May 2008 and December 2014, including 65 patients with CRT. Gastroscopy and pathological examination were conducted 4 weeks afterwards. The pathological responses were classified as complete response (CR) and non-CR. Serum samples were collected from the patients before radiotherapy, during week 4 of radiotherapy, and 1 week after radiotherapy. The VEGF changes were classified as increase, stable, and decrease.The median overall survival (OS) and median progression-free survival (PFS) in the pathological CR group was significantly longer than that of the non-CR group (P < .001). The 1-, 3-, and 5-year OS rates in the non-CR group were lower than that in the CR group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the non-CR group were lower than that in the CR group (P < .05). VEGF serum level was decreased during and after radiotherapy compared with pre-radiotherapy, and the differences were statistically significant (P < .05). The 1-, 3-, and 5-year OS rates in the increased group were lower than that in the decreasing group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the increasing group were lower than that in the decreasing group (P < .05). Pathological response (P < .05), serum VEGF trend (P < .05), and tumor-node-metastasis stage (P < .05) in response to CRT were factors that influenced patient prognosis.Pathological response and serum VEGF change during CRT can predict prognosis of nonsurgical patients with EC. Monitoring these changes is of significance in individualized treatment.

The Effect of the Leptin and Leptin Receptor Expression on the Efficacy of Neoadjuvant Chemotherapy in Breast Cancer.

BackgroundThe purpose of the present study was to evaluate the effect of leptin and leptin receptor (LEPR) expression on the efficacy of neoadjuvant chemotherapy in breast cancer.Material/MethodsThere were 325 breast cancer patients with complete data enrolled in this study. Patients were categorized into 3 groups: pathological complete response group, non-pathological complete response group, and progressive disease group. Immunohistochemistry was performed to determine leptin and its receptor LEPR expression levels that were compared among the 3 groups.ResultsCompared with the non-pathological complete response group, patients in the pathological complete response group had increased leptin and LEPR expression, although the difference was not statistically significant (P=0.194, P=0.110). In addition, the expression of leptin and LEPR in the pathological complete response group was also higher than that in the progressive disease group, and the difference of LEPR expression was statistically significant (P=0.008) while the leptin expression was not (P=0.065). There were more HER2+ breast cancer patients in the pathological complete response group categorized into strong positive, and positive expression of leptin and LEPR compared with the progressive disease group (P<0.05). There were significant differences of leptin and LEPR expression among breast cancer patients under different molecular subtypes HER2+, HR+, and triple negative, in which the triple negative patients had the highest expression of leptin and LEPR. In addition, patients in the progressive disease group had high and low expression of leptin and LEPR: 13.25% versus 11.32% and 13.1% versus 10.42% respectively.ConclusionsOverexpression of leptin and LEPR improved the therapeutic efficacy of neoadjuvant chemotherapy for patients with breast cancer, especially for those with HER2+ subtype. Overexpression of leptin and LEPR was distinct among the different molecular subtypes of breast cancer, suggesting a certain predictive value for breast cancer prognosis.

Factors Impacting Pathologic Complete Response after Neoadjuvant Chemotherapy in Breast Cancer: A Single-Center Study

Background: Neoadjuvant chemotherapy is the standard treatment for patients with locally advanced breast cancer which was recently introduced for operable breast cancer especially to achieve negative margins in breast conservation. Several studies have shown that Pathologic complete response (pCR) after neoadjuvant chemotherapy increases survival rate. The aim of this study therefore, was to evaluate the rate of pathologic complete response and its effective factors in breast cancer research center (BCRC). Methods: During a cross-sectional study, 179 patients with stage I to III breast cancer, who received neoadjuvant chemotherapy in breast cancer research center from 1997 to 2014, were included. Cases with pathologic complete response were defined as no tumor residue in the breast tissue and axillary region. This group of patients was compared with patients who had residual tumor at pathology. Data were analyzed by descriptive and inferential statistics using SPSS 19. Results: The mean age of patients was 45.4 years. Thirty-four patients (19%) were identified in the pathological complete response group (pCR). There was no significant difference between the pCR and non-pCR groups with respect to Age, Menopausal status, Family history of breast cancer, Tumor size, Histological type, Hormone receptors, Her-2neu and Phenotypic subtypes. However, ki67 index was significantly different between the two groups of patients, indicating that in patients with Ki67 of more than 40, pCR was the most observed (P = 0.01). Conclusions: This study showed that among the demographic, clinical, pathological and therapeutic factors, Ki67 can be a predicting factor for pathologic complete response after neoadjuvant chemotherapy.

PTV Hot-Spot Volume is Associated With Improved Pathologic Response After Neoadjuvant Stereotactic Body Radiation Therapy for Pancreatic Cancer

Stereotactic Body Radiation Therapy (SBRT) has been used in pancreatic adenocarcinoma (PCA) patients to improve local control but the optimal dose is unclear. At our institution, 6.6 Gy x 5 has been our standard prescription, with varying levels of “hot-spots” depending on patient anatomy. Our study aimed to characterize the hot-spot within the planning target volume (PTV) and investigate the association between hot-spot volume and surgical pathology response. Dose and volume relationships were queried for all PCA patients treated with neoadjuvant SBRT that underwent surgery at our institute from 2010 to 2016 from Oncospace. Patients whose PTV prescription was <30 Gy and went to surgery within 2 weeks from SBRT were excluded. PTV hot-spot (V35) was defined as PTV volume (cc) receiving at least 35 Gy, with the PTV defined as the gross target volume with a 2mm expansion. The primary outcome of complete response was characterized as 1) complete (CR), 2) near complete (NC), 3) moderate response (MR), and poor response (PR) from post-surgical resection by pathology review. Co-variates included chemotherapy duration (< 4 months vs ≥ 4 months), time from SBRT to surgery (weeks), active breathing control (ABC) status (free-breathing vs breath-hold), and GTV volume (cc). Ordinal logistic regression was performed to identify the association between V35 and pathologic outcomes. Of 120 patients who completed neoadjuvant SBRT underwent surgery, 102 were identified with criteria above. Among these patients, 58% (n = 60) received chemotherapy longer than 4 months, and 75% (n = 77) had breath-hold during treatment. Neoadjuvant pancreas SBRT was prescribed to a dose of 30 - 33 Gy in 5 fractions, the mean GTV size was 35 cc (range, 10 – 107 cc), and went to surgery within 8 weeks after SBRT (range, 2 – 27 weeks). Seven percent (n = 8) had a pathologic CR, 33% (n = 34) NC, 41% (n = 42) MR and 18% (n = 18) had PR. The dose coverage for hot-spot (V35) was 33cc (range, 5 – 99 cc). Among patients who were treated with active breath-hold, the mean V35 for CR, NC, MR and PR group were 50, 39, 30, 32 cc, respectively. Increased size of hot-spot (V35) was associated with improved pathologic complete response group (OR = 1.02, 95% CI 1 – 1.04, P = 0.05). Such correlation was not found among free-breathing patients. Size of hot-spot (V35) with ABC management suggests an association with improved pathologic response among neoadjuvant SBRT pancreatic cancer patients. Higher dose in free-breathing patients was not associated with local control perhaps due to larger targets with margin because of free-breathing status. Our analysis supports further dose escalation with ABC management during SBRT planning.

Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB) samples using high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

Downstaging After Chemoradiotherapy for Locally Advanced Rectal Cancer: Is There More (Tumor) Than Meets the Eye? Downstaging after chemoradiotherapy for locally advanced rectal cancer: is there more (tumor) than meets the eye?

Preoperative chemoradiotherapy can lead to pathologic complete response of rectal cancer. This study was designed to determine the relationship between postchemoradiotherapy pathologic T stage (ypT stage) and nodal metastases and to evaluate whether pathologic complete response of the primary tumor results in sterilization of mesorectal lymph nodes. Clinicopathological data from 1997 to 2007 of a prospectively maintained colorectal cancer database were examined. Inclusion criteria were patients with extraperitoneal rectal cancer who underwent preoperative chemoradiotherapy and subsequent radical resection. Statistical analysis was performed by use of Kruskall-Wallis and Wilcoxon rank-sum tests. Two hundred forty-two patients were identified (73.1% male, median age, 57 y (range, 36-85 y)). Data regarding preoperative chemoradiotherapy were available for 177 patients (73.1%). The median dose of radiotherapy was 5040 cGy (3060-6100 cGy). The mean preoperative radiotherapy dose and interval between chemoradiotherapy and surgery are similar when stratified by ypT stage (P = .55 and P = .72, respectively). Low anterior resection was performed in 174 patients (71.6%), and the remainder underwent abdominoperineal resection. A mural pathologic complete response was achieved in 62 patients (25.6%). In this pathologic complete-response group, positive lymph nodes were found in 2 patients (3.2%). The rate of metastatic lymph nodes increased as ypT stage increased (ypT1 = 11.1%, ypT2 = 29.2%, ypT3 = 37.3%). Patients with a mural pathologic complete response have a low rate of positive lymph nodes. These findings may have implications for the management strategies of these patients, including the use of local resection or a watch-and-wait policy. When the response to chemoradiotherapy is not complete, radical surgery should remain the treatment based on high rates of lymph node involvement.

Is Final TNM Staging A Predictor for Survival in Locally Advanced Rectal Cancer after Preoperative Chemoradiation Therapy?

Neoadjuvant chemoradiation therapy has improved the local control rate and overall survival in locally advanced rectal cancers. The purpose of this retrospective study is to evaluate the correlation between the final pathologic stage and survival in these patients. Patients with biopsy-proven rectal carcinoma, pretreatment staging by magnetic resonance imaging such as T3 or T4 tumors, or node-positive disease were treated with preoperative concomitant 5-fluorouracil-based chemotherapy and radiation, followed by radical surgical resection. Clinical outcome with survival, disease-free survival, recurrence rate, and local recurrence rate were compared with each T and N findings using the American Joint Committee on Cancer Tumor-Node-Metastasis (TNM) staging system. A total of 248 patients were enrolled in this study. Overall survival and disease-free survival at 1, 3, and 5 years were 97.1, 92, and 89.9% and 87.5, 71.1, and 69.5%, respectively. Thirty-six patients (14.5%) had a pathologic complete response after neoadjuvant therapy. The recurrence rate was significantly different between the pathologic complete response group and residual group (5.6 vs 31.1%; P = .002). Five-year disease-free survival was significantly better in the complete response group than the residual tumor group (93 vs 66%; P = .0045). There was no statistical difference in survival or locoregional recurrence rate between these two groups. Posttreatment pathologic TNM stage is correlated to disease-free survival and tumor recurrence rate in locally advanced rectal cancer after preoperative chemoradiation. Also, pathologic complete response to neoadjuvant treatment has its oncologic benefit in both overall recurrence and disease-free survival.