Pathological Response Of Primary Tumor Research Articles

Neoadjuvant tislelizumab with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-1): An open-label, single-arm, phase 2 study.

6073 Background: For patients with locally advanced head and neck squamous cell carcinoma (HNSCC), even receiving surgery with adjuvant radiotherapy or chemoradiotherapy, those remain at high risk of recurrence or metastasis. Neoadjuvant immunotherapy has been used in HNSCC, but provides only modest pathological response. Given single agent activity and unique mechanism of action of immune checkpoint inhibitors and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), we aimed to evaluate the antitumour activity and safety of neoadjuvant PD-1 blockade with EGFR inhibition in locally advanced HNSCC. Methods: This open-label, single-arm, phase 2 trial was done at a a tertiary hospital in China. Eligible patients were aged 18 years or older and had resectable HNSCC disease, had an Eastern Cooperative Oncology Group performance status of 0–1, had at least one measurable target lesion according to the RECIST 1.1, had no prior antitumor therapy for HNSCC. Patients received neoadjuvant treatment with intravenous tislelizumab (200 mg) on the first day of each 3 week, with totally two cycles and orally afatinib (30 mg) starting on the first treatment day and ending on the day before surgery, with totally six weeks, and then patients proceeded to receive surgical resection. The primary endpoint was major pathological response, defined as the presence of 10% or less residual viable tumour at the time of surgery. Results: A total of 25 patients were enrolled completed the neoadjuvant therapy. Eight of 23 evaluable patients exhibited a major pathological response (MPR) (35%; 95% confidence interval [CI], 16%—57%), of which four had a complete pathological response of primary tumor (17%, 95%CI, 5%—39%). The overall response rate was 48% (12/25, 95%CI: 28%—69%) and disease control rate was 100% (25/25, 95%CI: 86%—100%). Common grade 3—4 adverse events included diarrhea (5/25 [20%]), hypokalemia (4/25 [16%]) and rash (3/25 [12%]). No treatment related fatalities were observed. Immunologically, post-neoadjuvant treatment demonstrated increased CD3, CD8, and CD56 expression within the tumor microenvironment. The increase of CD8 and CD56 expression level was significant higher in patients achieving MPR, along with elevated circulatory NK cells at baseline, compared to those in patients achieving non-MPR. Conclusions: This study underscores encouraging antitumor activity, manageable toxicity profile and promising immune activation elicited by neoadjuvant tislelizumab plus afatinib for HNSCC, which deserves further assessment. Clinical trial information: NCT05517330 .

The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy

ObjectiveTo explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer. MethodsEighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology. ResultsIDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176–10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234–11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis. ConclusionIDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.

A Comparison of Clinicopathologic Outcomes and Patterns of Lymphatic Spread across Neoadjuvant Chemotherapy, Neoadjuvant Chemoradiotherapy and Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma

To evaluate the differences in pathologic complete response (pCR) rates, TRG score, pathologic T stage and the pattern of lymphatic spread among patients receiving neoadjuvant chemotherapy (NCT) or neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant immunochemotherapy (NICT) prior to esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC). A total of 702 patients with ESCC who completed transthoracic esophagectomy followed neoadjuvant therapy at three cancer centers from January 2017 to December 2022 were enrolled. Among the included patients, 382 patients were treated with NCR, 172 with NCRT, and 148 with NICT. Inverse probability of treatment weighting (IPTW) was performed to control potential confounding factors. Pathological response of primary tumor was evaluated using the Chirieac modified tumor regression grade (TRG) system. The complete regression of primary lesion and nodal metastases were considered pCR. Lymph node classification system used the 8th edition of AJCC. Specimens were assessed for pattern of lymphatic spread. After adjusting for baseline characteristics, the R0 resection rate did not significantly differ between the patients receiving NCT or NCRT or NICT (99.48% vs.100% vs.98.65%, P = 0.273). Compared with the NCT group, the NCRT group and NICT group had an advantage in pathological response (P<0.05). The pCR rate was 7.07% in the NCT group, 30.23% in the NCRT group, and 22.30% in the NICT group. Compared to the other two groups, the TRG score (P<0.05) and pathologic T stage (P<0.05) in the NCT group were significantly higher. In the NCT group, 9.97% had ypT0 disease, compared with 35.76% in the NCRT group and 25.68% in the NICT group. And in the NCT group, 9.71% had TRG1 disease, compared with 32.76% in the NCRT group and 25% in the NICT group. Compared with NICT, NCRT can significantly reduce the rate of LNM in station 1R (0 vs 3.38%, P<0.05) and 2R (1.15% vs 6.76%, P<0.05). Subgroup analysis according to the tumor location distribution showed that in upper thoracic cases, there was no statistical difference in LNM rates among stations no matter whether patients received NCT or NCRT or NICT. NICT group had higher LNM rates in station 2R (9.1%) in middle thoracic cases (P<0.05) and in station 18 (7.5%) (P<0.05) in lower thoracic cases, compared with the NCRT group and NCT group. NCRT or NICT followed by surgery may result in a promising pCR rate and show a better performance in therapeutic response of primary lesion. No matter whether patients received NCT or NCRT or NICT, multiple level and skip node metastases are common, and adequate lymphadenectomy should be achieved to ensure the complete removal of metastatic lymph nodes.

Comparison of the predictive value of pathological response at primary tumor and lymph node status after neoadjuvant chemotherapy in locally advanced gastric cancer.

Preoperative chemotherapy has been increasingly used in locally advanced gastric cancer (LAGC). However, the prognostic factors are still insufficient. This study aimed to investigate the prognostic significance of pathological response of the primary tumor to neoadjuvant chemotherapy (NACT) and the lymph node status after NACT. Data from 160 patients with LAGC treated with NACT followed by gastrectomy and met the inclusion criteria between March 2016 and December 2019 were retrospectively reviewed. Pathological evaluation after NACT was based on the grade of pathological response of the primary tumor and the status of lymph node. Survival curves for overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. Among 160 selected cases, 90 had pathological response (PR), while 70 had no pathological response (nPR) to NACT. Smaller tumor size was presented in PR group, which also had lower level of signet ring cell features, compared to nPR group (all p < 0.05). Based on the status of lymph nodes, nodal status (-) group showed smaller tumor size, lower depth of tumor invasion, better differentiated degree, lower level of signet ring cell features, lower rate of lymphatic and venous invasion and less advanced ypTNM stage (all p < 0.05). Survival was equivalent between PR and nPR group (all p > 0.05), while patients with no lymph node metastasis had better DFS than that with lymph node metastasis (HR 0.301, 95% CI 0.194-0.468, p = 0.002). Multivariable Cox regression analysis identified that lymph node status after NACT was an independent prognostic factor associated with survival (OS: hazard ratio 1.756, 95% CI 1.114-3.278, p = 0.029; DFS: hazard ratio 1.901, 95% CI 1.331-3.093, p = 0.012). Lymph node status is a potential independent prognostic factor for LAGC patients treated with NACT and may be more efficient than pathological response in primary tumor.

Can adjuvant radiotherapy be omitted for oral cavity cancer patients who received neoadjuvant therapy and surgery? A retrospective cohort study.

Surgery and postoperative adjuvant therapy comprise the standard treatment for locally advanced resectable oral squamous cell carcinoma (LAROSCC), while preoperative neoadjuvant therapy is being explored without sufficient confirmation of improved survival. De-escalation regimens after neoadjuvant therapy, such as those omitting adjuvant radiotherapy, may provide comparable or better outcomes, suggesting rigorous assessment of adjuvant therapy outcomes is needed in LAROSCC patients. The authors thus performed this retrospective study in LAROSCC patients who received neoadjuvant therapy and surgery, to compare the outcomes for overall survival (OS) and locoregional recurrence-free survival (LRFS) between the adjuvant radiotherapy (radio) and nonradiotherapy (nonradio) cohorts. Patients diagnosed with LAROSCC who received neoadjuvant therapy and surgery were enrolled and divided into radio and nonradio cohorts to determine whether adjuvant radiotherapy could be omitted after neoadjuvant therapy and surgery. From 2008 to 2021, 192 patients were enrolled. No significant differences were found in OS or LRFS between the radio and nonradio patient cohorts. The 10-year estimated OS rates were 58.9 versus 44.1% in radio versus nonradio cohorts, while 10-year estimated LRFS rates were 55.4 versus 48.2%, respectively. For clinical stage III patients, 10-year OS rates were 62.3 versus 62.6% (radio vs. nonradio), and estimated 10-year LRFS rates were 56.5 versus 60.7% (radio vs. nonradio). Multivariate Cox regression modeling of postoperative variables showed pathologic response of primary tumor and pathologic regional lymph nodes staging were associated with survival, while the adjuvant radiotherapy exposure was not included in the model due to nonsignificance. These findings support further prospective evaluation of adjuvant radiotherapy omission, and suggest that de-escalation trials are warranted for LAROSCC surgery patients who received neoadjuvant therapy.

Pathologic responses and surgical outcomes after neoadjuvant immunochemotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC. Of 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors. After adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062). For patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs.

Diffusion-weighted MRI and 18F-FDG PET/CT in assessing the response to neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

BackgroundNeoadjuvant chemoradiotherapy (nCRT) followed by surgery is a currently widely used strategy for locally advanced esophageal cancer (EC). However, the conventional imaging methods have certain deficiencies in the evaluation and prediction of the efficacy of nCRT. This study aimed to explore the value of functional imaging in predicting the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal squamous cell carcinoma (ESCC).MethodsFifty-four patients diagnosed with locally advanced ESCC from August 2017 to September 2019 and treated with nCRT were retrospectively analyzed. DW-MRI scanning was performed before nCRT, at 10–15 fractions of radiotherapy, and 4–6 weeks after the completion of nCRT. 18F-FDG PET/CT scans were performed before nCRT and 4–6 weeks after the completion of nCRT. These 18F-FDG PET/CT and DW-MRI parameters and relative changes were compared between patients with pathological complete response (pCR) and non-pCR.ResultsA total of 8 of 54 patients (14.8%) were evaluated as disease progression in the preoperative assessment. The remaining forty-six patients underwent operations, and the pathological assessments of the surgical resection specimens demonstrated pathological complete response (pCR) in 10 patients (21.7%) and complete response of primary tumor (pCR-T) in 16 patients (34.8%). The change of metabolic tumor volume (∆MTV) and change of total lesion glycolysis (∆TLG) were significantly different between patients with pCR and non-pCR. The SUVmax-Tpost, MTV-Tpost, and TLG-Tpost of esophageal tumors in 18F-FDG PET/CT scans after neoadjuvant chemoradiotherapy and the ∆ SUVmax-T and ∆MTV-T were significantly different between pCR-T versus non-pCR-T patients. The esophageal tumor apparent diffusion coefficient (ADC) increased after nCRT; the ADCduring, ADCpost and ∆ADCduring were significantly different between pCR-T and non-pCR-T groups. ROC analyses showed that the model that combined ADCduring with TLG-Tpost had the highest AUC (0.914) for pCR-T prediction, with 90.0% and 86.4% sensitivity and specificity, respectively.Conclusion18F-FDG PET/CT is useful for re-staging after nCRT and for surgical decision. Integrating parameters of 18F-FDG PET/CT and DW-MRI can identify pathological response of primary tumor to nCRT more accurately in ESCC.

Lauren Classification Is A Predictor For Pathological Response Of Preoperative Chemoradiotherapy Compared With Preoperative Chemotherapy In Patients With Locally Advanced Gastric Cancer

To investigate the predictive value of Lauren classification to tumor pathological response after preoperative chemoradiotherapy (CRT) vs. preoperative chemotherapy (ChT) in locally advanced gastric adenocarcinoma (LAGC). From June 2013 to Dec, 2019, 182 patients in our hospital were enrolled into an ongoing multicentric phase III clinical trial comparing preoperative CRT (induction XELOX × 1 + 45Gy/25f with concurrent dose-reduced XELOX × 2) with preoperative ChT (XELOX × 3) in LAGC (NCT01815853). The clinical stage should be cT3N2-3M0, cT4aN+M0, or cT4bNanyM0. There were 124 males and 58 females, median age was 60 yrs (range 26-75 yrs). The interval between end of RT and surgery was 6-8 weeks. 65 out of 91 patients in the ChT group and 61 out of 91 patients in the CRT group had completed the preoperative treatments and the following radical D2 gastrectomy. Pathological response of primary tumor was categorized with NCCN tumor regression grade (TRG). Favorable pathological response (FPR) was defined as TRG0-1 with ypN0. At enrollment, patients’ baseline and tumor characteristics were well-balanced between the two groups. Proximal GC was in 58.2% (53/91) and 50.5(46/91) of the CRT and ChT group, respectively. Intestinal type (IT) GC was identified in 33(36.3%) patients of the ChT group, and in 36(39.6%) patients of the CRT group (X2 = 0.51, p = 0.916). After D2 gastrectomy, proportions of IT were 32.3% (21/65 pts) in the ChT group, and 50.8% (31/61 pts) in the CRT group, showing obvious shift towards resectability favoring IT vs. non-intestinal (n-IT, diffused plus mixed) type (X2 = 8.61, P = 0.035) after CRT. CRT group achieved higher rate of pCR (21.3% vs 3.1%, P = 0.002). There were 30, 37, and 22 patients obtained TRG0-1, ypN0, and FPR, respectively in the CRT group, while only 10, 14, and 5 patients did in the ChT group (P<0.001 for all). In the CRT group, ypN0 and FPR were observed in 80.6% and 45.2% of patients with IT tumor, but only in 35.7% and 21.4% with n-IT tumors (ypN0:P<0.001; FPR: P = 0.054), respectively. Logistic regression revealed IT tumor with higher probability of achieving ypN0 (OR = 7.500, 95%CI: 1.838-30.730; P = 0.005) than n-IT tumors. In contrast, no such differences were observed in the ChT group. Primary tumor locations were not predictive for ypN0 or TRG. In all patients with IT tumors, CRT was associated with higher rates of TRG0-1 (51.6% vs. 14.3%, P = 0.006), ypN0 (80.6% vs. 19.0%, P<0.001), FPR (45.2% vs. 0%, P<0.001) , pCR (22.6% vs. 0%, P = 0.033), and upstage 0-II (93.5% vs. 50.0%, P = 0.001) than ChT, while in patients with n-IT GC, only TRG showed significant improvement favoring CRT than ChT(TRG0-1: 42.9% vs. 15.9%, P = 0.011). Intestinal type gastric adenocarcinomas showed better responses to preoperative CRT vs. preoperative ChT than diffuse or mixed type GC did. This is the first set of data to date suggesting the predictive value of Lauren classification to tumor response after preoperative treatment in gastric cancer.

Abstract 6498: Preoperative treatment remodels immune microenvironment via decreasing pro-tumorigenic and increasing anti-tumorigenic immune cells in the locally advanced gastric cancer

Abstract Purpose: To investigate the immune response in the tumor microenvironment and the association between immune response and pathological response after preoperative chemotherapy or preoperative chemoradiotherapy for locally advanced gastric cancer. Experimental Design:123 patients with locally advanced gastric cancer with or without preoperative treatment were analyzed by immunohistochemistry for CD4, CD45RO, FOXP3 and PD-L1. 83 of the 123 patients completed preoperative treatment and radical gastrectomy in our hospital between June 2013 and September 2019, which belonged to an ongoing multicentric randomized phase III clinical trial comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer (NCT01815853). They were 41 patients in the preoperative chemoradiotherapy (CRT) group, and 42 patients in the preoperative chemotherapy (ChT) group. The other 40 patients underwent surgery first without preoperative treatment (Surgery First group: SF) matched according to clinical pathological characteristics with the CRT and ChT group. T-cell subset densities both within tumor area and at the invasive front were analyzed using slide digital imaging and automated and software-based quantification algorithms. Pathological response of primary tumor was analyzed according to the NCCN tumor regression grade (TRG). The differences of T-cell subset densities and PD-L1 status among three groups and the relationship between these differences and tumor regression was evaluated. Results: The patients’ baseline and tumor characteristics were well-balanced among CRT, ChT, and SF groups. 28 patients obtained TRG0-2 in CRT group (n=41), in contrast, only 18 patients obtained TRG0-2 in ChT group (n=42; P=0.020). The number of FOXP3+ T cell and CD45RO+ T cell infiltrations was significantly lower in the CRT group (tumor area: P&amp;lt;0.001, P=0.011 respectively; invasive front: P&amp;lt;0.001, P&amp;lt;0.001 respectively) or ChT group (tumor area: P&amp;lt;0.001, P=0.033 respectively; invasive front: P&amp;lt;0.001, P=0.001 respectively) comparing with SF group. In contrast, the number of CD8+ T cells in tumor invasive front was significant higher in the CRT group (P&amp;lt;0.001) or ChT group (P=0.002) comparing with SF group. Addition of radiation to preoperative chemotherapy (CRT) significantly decreased PD-L1 expression in tumor cells (CRT group vs. ChT group: 14.6% vs. 35.7%, P=0.027). However, no differences of T cell infiltrations and PD-L1 expression in immune cells between CRT group and ChT group were observed. In CRT group, lower FOXP3+ cell density in tumor area (P&amp;lt;0.001) and invasive front (P=0.009), higher CD8+ cell density (P=0.040) and CD45RO+ T cell density (P=0.045) in tumor area were strongly associated with higher probability of achieving TRG0-2. In ChT group, lower FOXP3+ cell density in tumor area (P=0.027) and higher CD8+ cell density (P=0.040) in invasive front were significantly associated with higher probability of achieving TRG0-2. Conclusions: Preoperative treatment in locally advanced gastric cancer is useful for reducing regulatory T cell levels and increasing cytotoxic T cell levels. CRT and ChT may not only be cytotoxic, but have pleiotropic and beneficial effects on the tumor microenvironment. Citation Format: Yi Fang, Yujing Zhang, Nai Li, Yihong Ling, Zhiwei Zhou. Preoperative treatment remodels immune microenvironment via decreasing pro-tumorigenic and increasing anti-tumorigenic immune cells in the locally advanced gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6498.

Outcome if Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Tertiary Care 11 Center Experience

Background: Breast cancer is the most common cancer of Bangladeshi women. Almost allpresent with palpable lump and 40% of them are with locally advanced breast cancer.Neoadjuvant chemotherapy is the standard choice of treatment for the patients.&#x0D; Objective: To observe the clinical and pathological response of locally advanced breastcancer after four cycles of chemotherapy and surgery.&#x0D; Methods: This prospective study was carred over the newly diagnosed locally advancedbreast cancer (LABC) patients from January 2010 to December 2014. Before going toneoadjuvant chemotherapy each patient was evaluated clinically, radiologically and withother relevant investigations. The size of primary tumor and axillary node was measured andrecorded. Chemotherapy schedule with Cyclophosphamide 600mg/m2 and Doxorubicin60mg/m2 (AC) and compared with the previous record. After 3-4 weeks of completion ofchemotherapy, the patients was prescribed and carried out three weekly for four cycles.Primary tumor size and axillary nodal size was measured who were undergone mastectomyand axillary dissection. Histopathology was done to see then the pathological response ofprimary tumor and axillary node. Other biological marker such as estrogen receptor (ER),progesterone receptor (PR) and Human epidermal growth receptor (HER-2) was done. Aftercompletion of study the data was compiled and analyzed.&#x0D; Results: Total 220 cases of LABC were enrolled in this study. After four cycles of chemotherapywith AC, 194 patients (88%) responded clinically, 29 patients (13%) showedcomplete clinical response (cCr)-and 165 patients (75%) partial response (pCr). Surgicalspecimen showed complete pathological response (cPr) in 22 patients (10%).&#x0D; Conclusion: Neoadjuvant chemotherapy with AC is the standard chemotherapy schedule forlocally advanced breast cancer and radical surgery was possible in 75% of the patients.&#x0D; Journal of Surgical Sciences (2016) Vol. 20 (1) : 13-17

Impact of Genetics on Neoadjuvant Therapy with Complete Pathological Response in Metastatic Colorectal Cancer: Case Report and Review of the Literature.

Treatment of colorectal metastatic cancer is still challenging, despite recent improvements in chemotherapy. A genetic cancer profile, such as the KRAS (Kirsten rat sarcoma) gene status, plays a key role in individualized tailored therapy. Molecular targeted therapy added to neo-adjuvant chemotherapy can achieve a better pathological response and prolong survival. Pathological complete response of colorectal cancer stage IV is rare. A 47-year-old female patient presented with rectal adenocarcinoma and three liver metastases (cT3d/4, N2, Ml). After seven cycles of Bevacizumab and CAPOX in neoadjuvant setting, we noted more than 70.0% regression of metastases and complete regression of the primary tumor. We performed low anterior resection of rectum and synchronous subsegmental resection of S3, because the other two lesions were not detectable. Pathology revealed complete response of the primary and also secondary tumors. After 8 months, diagnostic tests did not show any sign of recurrence and the remaining liver lesions disappeared. Colorectal cancer is a heterogeneous disease and it is necessary to identify patients who are at-risk of recurrence and suitable for neoadjuvant therapy. Genetic biomarkers play an important role in metastatic colorectal cancer treatment. Because of the mutated KRAS gene, Bevacizumab was added to cytotoxic therapy achieving a complete pathological response of primary tumor and metastasis. This case is unique because all reported cases with similar results, described staged surgery and one of reverse staged surgery, but with similar results. This neoadjuvant therapy has extraordinary results for colorectal cancer stage IV and can help disease-free and long-term survival.

Outcome of neoadjuvant chemotherapy in locally advanced breast cancer: A tertiary care center experience

Breast cancer is the most common cancer among Bangladeshi women. Almost all present with palpable lump and 40% of them are with locally advanced breast cancer. Neoadjuvant chemotherapy is the standard choice of treatment for the patients.This prospective study was done involving 220 newly diagnosed locally advanced breast cancer (LABC) patients from January 2010 to December 2014 in the National Institute of Cancer Research &amp; Hospital (NICRH), Mohakhali, Dhaka to observe the clinical and pathological response of locally advanced breast cancer after four cycles of chemotherapy and surgery. Chemotherapy schedule with Cyclophosphamide 600mg/m2 and Doxorubicine 60mg/m2 (AC) was prescribed and carried out three weekly for four cycles. Primary tumor size and axillary nodal size was measured and compared with the previous record. After three weeks of chemotherapy the patients undergone mastectomy and axillary dissection. Histopathology was done to see the pathological response of primary tumor and axillary node. Other biological marker such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor (HER-2) were done. After four cycles of chemotherapy with AC, 194 patients (88%) responded clinically, 29 patients (13%) showed complete clinical response (cCr) and 165 patients (75%) partial response (pCr). Surgical specimen showed complete pathological response (cPr) in 22 patients (10%). Neoadjuvant chemotherapy with AC is the standard chemotherapy schedule for locally advanced breast cancer and radical surgery was possible in 75% of the patients.Bangladesh Med J. 2016 Sep; 45 (3): 141-146

The predictive value of 18F-FDG PET for pathological response of primary tumor in patients with esophageal cancer during or after neoadjuvant chemoradiotherapy: a meta-analysis.

We want to review the value of 18-fluoro-deoxy-glucose positron emission tomography for response prediction of primary tumor in patients with esophageal cancer during or after neoadjuvant chemoradiotherapy. Studies were searched in Pubmed, Embase and Cochrane Library with specific search strategy. The published articles were included according to the criteria established in advance. The included studies were divided into two groups according to the time of the repeat positron emission tomography: during (Group A) or after neoadjuvant chemoradiotherapy (Group B). The studies that performed the repeat positron emission tomography after neoadjuvant chemoradiotherapy were graded Quality Assessment of Diagnostic Accuracy Studies. The pooled sensitivity, specificity and diagnostic odds ratio were obtained for both groups on the basis of no-existing of threshold effect. Fifteen studies were included in the present study. The threshold effect did not exist in both groups. The pooled sensitivity, specificity and diagnostic odds ratio were 85%, 59%, 6.82 with 95% confidence interval 76-91%, 48-69%, 2.25-20.72 in Group A. The equivalent values were 67%, 69%, 6.34 with 95% confidence interval 60-73%, 63-74%, 2.08-19.34 in Group B. The pooled sensitivity was 90% in four studies that enrolled patients with esophageal squamous cell carcinoma merely in Group B. According to the present data, positron emission tomography should not be used routinely to guide treatment strategy in esophageal cancer patients. We speculated that positron emission tomography could be used as a tool to predict treatment response after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

The Impact of Pathological Response of Primary Tumor in Patients With Locally Advanced Breast Cancer Who Reached Axillary Pathological Complete Response (pCR) After Neoadjuvant Chemotherapy

The Impact of Pathological Response of Primary Tumor in Patients With Locally Advanced Breast Cancer Who Reached Axillary Pathological Complete Response (pCR) After Neoadjuvant Chemotherapy

Impact on Radiological and Pathological Response with Neoadjuvant Chemoradiation and Its Effect on Survival in Squamous Cell Carcinoma of Thoracic Esophagus.

Neoadjuvant chemoradiation (NCRT) has been shown to improve survival in patients with locally advanced esophageal squamous cell carcinoma (SCC). The aim of the present study was to evaluate the role of 18-FDG PET-CT in predicting pathological response to NCRT. We assessed 70 patients of esophageal SCC who underwent NCRT and were evaluated with baseline and post chemoradiation 18F-FDG PET-CT scan. Receiver operating characteristic (ROC) curve was generated by analyzing the sensitivity and specificity of different cut-off points for defining a positive test and their ability to predict pathological complete response. Univariate and multivariate analysis were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. Radiological and pathological complete response was achieved in 44.3% (n=31) and 34.3% (n=24) patients, respectively. Using ROC curves, post-treatment standardized uptake value (SUV) max [3.25, area under curve (AUC) 0.752] and % change in SUVmax cut-off value (72.32%, AUC 0.705) was used to predict pathological response. Significant associations between pathological response in primary tumor and post chemotherapy/radiotherapy SUVmax values (p=0.016), % change in SUVmax (p=0.006), radiological response in primary (p=0.006), and grade of dysphagia at presentation (p=0.041) were observed. Mean overall survival and relapse free survival was 83 and 58%, respectively at 34months. 18F-FDG PET-CT can be used to predict pathological response to NCRT in locally advanced SCC.

Implications for selecting local excision in locally advanced rectal cancer after preoperative chemoradiation.

Local excision may offer the possibility of organ preservation for the management of locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT). However, the oncological outcomes of this strategy have been largely associated with the risk of nodal metastases. In this study, Surveillance, Epidemiology, and End Results Program (SEER)-registered rectal cancer patients, and patients from Fudan University Shanghai Cancer Center (FUSCC) after preoperative chemoradiation were combined to analyze the incidence of lymph node metastasis. The results showed that there was a high risk for residual lymph node metastasis among patients even with complete pathologic response of primary tumor after preoperative CRT (12.6-13.2%). However, in the selected group of patients with pre-CRT MRI staging cN0 rectal cancer, there was only one ypN+ case (3.3%) in ypT0-1 group. These results suggest that pre-CRT MRI staging cN0 patients achieved ypT0-1 of bowel wall tumor may be suitable for local resection.

D2 lymphadenectomy is not only safe but necessary in the era of neoadjuvant chemotherapy

BackgroundPatients with locally advanced resectable gastric cancers are increasingly offered neoadjuvant chemotherapy (NACT) following the MAGIC and REAL-2 trials. However, information on the toxicity of NACT, its effects on perioperative surgical outcomes and tumor response is not widely reported in literature.MethodsAnalysis of a prospective database of gastric cancer patients undergoing radical D2 gastrectomy over 2 years was performed. Chemotherapy-related toxicity, perioperative outcomes and histopathological responses to NACT were analyzed. The data is presented and compared to a cohort of patients undergoing upfront surgery in the same time period.ResultsIn this study, 139 patients (42 female and 97 male patients, median age 53 years) with gastric adenocarcinoma received NACT. Chemotherapy-related toxicity was noted in 32% of patients. Of the 139 patients, 129 underwent gastrectomy with D2 lymphadenectomy, with 12% morbidity and no mortality. Major pathological response of primary tumor was noted in 22 patients (17%). Of these 22 patients, lymph node metastases were noted in 12 patients. The median blood loss and lymph node yield was not significantly different to the 62 patients who underwent upfront surgery. Patients who underwent upfront surgery were older (58 vs. 52 years, P <0.02), had a higher number of distal cancers (63% vs. 82%, P <0.015) and a longer hospital stay (11 vs. 9 days, P <0.001).ConclusionsPerioperative outcomes of gastrectomy with D2 lymphadenectomy for locally advanced, resectable gastric cancer were not influenced by NACT. The number of lymph nodes harvested was unaltered by NACT but, more pertinently, metastases to lymph nodes were noted even in patients with a major pathological response of the primary tumor. D2 lymphadenectomy should be performed in all patients irrespective of the degree of response to NACT.

What is the Incidence of Metastatic Lymph Node Involvement After Significant Pathologic Response of Primary Tumor Following Neoadjuvant Treatment for Locally Advanced Rectal Cancer?

In locally advanced rectal cancer (LARC) patients, major response to neoadjuvant radiotherapy (NR) has been associated with favorable long-term outcomes. Positive pathologic nodal status was recently proven to be associated with poor prognosis even after total regression of primary tumor (ypT0). The aim of this study was to evaluate the rate of lymph node (LN) involvement in patients with complete (ypT0) or major (TRG1: very few viable tumor cells) response. Included were patients with complete or major response after radiotherapy followed by surgery and histological examination of the whole specimen. From 1996 to 2010, 245 patients with LARC were treated by NR. We collected clinical data for 53 patients (21.6 %) with ypT0 (n = 26, 49 %) or TRG1 (n = 27, 51 %) response. Sphincter-preserving surgery was performed in 40 patients (75 %). Overall, nine patients (16.9 %) presented LN involvement: 2 (7.7 %) in the ypT0 group and 7 (25.9 %) in the TRG1 group (NS). Patients with ypT3 tumors had significantly more invaded LN than patients with ypT1-T2 tumors (6 of 13 [46 %] vs 1 of 14 [7 %], p = .032). After median follow-up of 30 months (range, 1-160 months), 5-year disease-free and overall survivals were 88.2 and 89.0 %, respectively. There was a clear cutoff between patients with ypT0-T2 (3 of 40, 7.5 %) and ypT3 (6 of 13, 46 %) concerning the incidence of metastatic LN in patients achieving pathologic complete or major response after NR. In patients with good clinical response, local full-thickness resection of the residual tumor could be a first step, followed by standard rectal resection in cases of ypT3.

Primary tumor resection to improve survival and local disease control in stage IV inflammatory breast cancer.

1102 Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer typically presenting with early metastasis. Optimal outcomes are achieved with multimodality treatment strategies in the non-metastatic setting. Data is limited, however, on the benefit of surgery in patients with metastatic IBC. We evaluated the effect of primary tumor resection on outcomes in patients with newly diagnosed stage IV IBC. Methods: We reviewed records of 172 patients with metastatic IBC treated at our institution from 1994 - 2009. All patients received systemic therapy with or without locoregional therapy (LRT). Patient demographics, receptor (ER) and HER2-neu status, grade, histology, presence of lymphovascular invasion, margin status, number of distant disease sites, pathologic response of primary tumor and clinical response to systemic therapy (CRS) at distant disease sites were recorded. Overall survival (OS), distant progression-free survival (DPFS), and chest/skin involvement at last follow-up were evaluated. Kaplan-Meier survival analyses, univariate (UV) and multivariate (MV) logistic regression models were used. Chest/skin involvement was compared between groups using Kruskal-Wallis test. Results: Seventy-nine (45%) patients underwent primary tumor resection. Average age was 51 (22-78). Median live-patient follow-up was 33 months. OS and DPFS were significantly better for patients who underwent LRT versus none (p&lt;0.0001). Factors associated significantly for improved DPFS on MV analysis were ER and HER2-neu status (HR 0.61,0.60 p=0.02,0.05 ,respectively), LRT (HR .38, p=0.002) and CRS (HR 0.62, p=0.03). ER status (HR .45, p&lt;0.001), LRT (HR .30, p&lt;0.001) and CRS (HR 0.54, p=0.02) were significant predictors for higher OS on MV analysis. At last follow up, chest/skin involvement was moderate/severe in 11% of patients in LRT group versus 35% of patients in no LRT group (p&lt;0.0001). Conclusions: This latest retrospective study demonstrates metastatic IBC patients who undergo LRT in addition to systemic therapy may have improved survival and local control outcomes. CRS may be used to guide LRT. A prospective randomized trial is needed to validate these findings.

Study on predictors of long term results for neo-adjuvant chemotherapy in locally advanced breast cancer

To identify predictive markers of the long-term outcome for neo-adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with intravenous vinorelbine (V) and epirubicin (E) combination regimen. One hundred and nineteen patients with LABC were treated from September 2001 to May 2006. All patients were diagnosed as invasive breast cancer by 14G core needle biopsy and treated with three cycles of VE regimen before the operation. The patients were subjected to surgery and subsequently were given other three cycles of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the clinical responses. Local-regional radiotherapy was applied to all patients after the chemotherapy and followed by hormone-therapy according to hormone receptor status. The impact of clinical, pathological, and immunohistochemical features on disease free survival (DFS) and overall survival (OS) was evaluated. All patients were evaluable for responses: clinical complete response was documented in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response. The pathological complete response was found in 22 cases (18.5%). Of the patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%, respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67 expression (P=0.045), no pathological complete response after NC (P=0.034) were associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological complete response after NC (P=0.034) were associated with a shorter survival. Pathological response in primary tumor, pre-Ki-67 and post-Ki-67 expression, pre-ER expression are important predictors of long-term outcome for LABC patients with three cycles of VE regimen before operation.