Good Tumor Response Research Articles

Abstract P4-01-12: The association of circulating tumor cells with tumor response in breast cancer patients undergoing neoadjuvant chemotherapy

Abstract Introduction Despite its limitations, Cellsearch® remains the only validated technique to detect circulating tumors cells (CTCs) in the peripheral blood of cancer patients. A new technique (CytoFind) allows trapping CTCs with varied numbers of antigen-targeted magnetic particles to be trapped in different compartments of a fluidic chip based on their level of expression and velocity, allowing the detection and count of CTC subpopulations (profiling-based technique). Additionally, this technique is able to use different capture agents for binning and profiling beside the EpCAM expression. We used magnetic nanoparticles tagged with anti-Her2 in a new microfluidic device to capture CTCs (Her2 technique). We aimed to prospectively assess the performance of this new technology compared to Cellsearch® and evaluate the association of CTCs with tumor response in breast cancer patients on neoadjuvant chemotherapy. Methods Breast cancer patients who underwent neoadjuvant chemotherapy followed by surgery were eligible. CTCs were enumerated before the start of neoadjuvant chemotherapy. The concordance of CTC detection between techniques was assessed with the intraclass correlation coefficient (ICC). The association between CTCs and baseline characteristics as well as tumor response was evaluated with a Fisher exact test. Tumor response was assessed as pathologic complete response (pCR) and with the residual cancer burden index (RCB). Results Thirty-five patients were successfully assessed for CTCs using at least one technology. Fifty four percent and 23% of the patients had a HER2 positive and triple negative disease respectively. Thirty eight percent and 53% of the patients had a pCR and a good tumor response rate (RCB 0 or 1) respectively. The mean CTC count detected was 0.63 (SD 1.8), 0.71 (SD 1.51) and 1.22 (SD 1.62) with Cellsearch®, profiling-based and Her2 technologies respectively. An association was seen between detected CTCs and tumor size as well as progesterone receptor status (p<0.05) but not with the rest of the baseline characteristics: age, estrogen receptor, Her2, or nodal status, tumor grade and presence of lymphovascular invasion (p>0.05). No association was found between CTC counts and tumor response (pCR or RCB). The profiling-based and Her2 technologies were moderately concordant (ICC=0.5) but a low concordance with Cellsearch® was observed (ICC=0.07). Conclusions A new profiling-based technology detected CTCs in breast cancer patients and may overcome the Cellsearch® limitations and provide more information on CTCs subpopulations. Yet, further calibration and validation are needed before using this technology in future research. While no association between CTCs and tumor response was observed, a longer follow up is needed to assess the impact on survival. Citation Format: Jacques Raphael, Reza Mohamadi, Alex Kiss, Maureen Trudeau, Sunil Verma, Alison Allan, Shana Kelley, Joelle Helou, Fang-I Lu, Siqi Zhu, Kathleen I Pritchard. The association of circulating tumor cells with tumor response in breast cancer patients undergoing neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-01-12.

Predictive value of serum and tissue carcinoembryonic antigens for radiologic response and oncologic outcome of rectal cancer

PurposeThe clinical importance of tissue CEA levels for predicting tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer has not been studied. MethodsSerum CEA levels and tissue CEA expressions for 117 patients who underwent preoperative CRT for rectal cancer, were prospectively collected and analyzed at a tertiary university hospital ResultsThe median follow-up time was 49 months (range, 3–61 months), and the 5-year disease-free survival (DFS) rate was 68.3 %. In multivariate analysis, serum CEA (log-transformed value) [odds ratio (OR) = 0.741, 95 % confidence interval (CI) 1.588–40.422, P = 0.021], tissue CEA/GAPDH ratio (OR = 3.673, 95 % CI 1.316–12.081, P = 0.019), and tumor circumferentiality (OR = 2.960, 955 CI, 1.101–8.999, P = 0.040) were the independent predictors for good tumor response to CRT. Serum CEA level was significant prognostic factor for DFS (P = 0.004) in multivariate analysis. However, tissue CEA was not associated with DFS. ConclusionsBoth serum and tissue CEA were significant factors for predicting good tumor response following preoperative CRT. However, tissue CEA was not associated with the oncologic outcome. The possibility of radiologic resistance of high CEA tumors is expected to be investigated through further studies.

When Can We Avoid Postmastectomy Radiation Following Primary Systemic Therapy?

Postmastectomy radiation therapy (PMRT) has been shown to reduce the risk of locoregional recurrences (LRR) and of distant metastases (DM) and to improve breast cancer-specific survival (BCSS) as well as overall survival (OS) in patients with locally advanced breast cancer who are considered high risk because of large tumors (> 5cm) and/or presence of axillary lymph node involvement. Controversy is still ongoing with respect to the indication of PMRT in the case of earlier stage invasive tumors in the presence of risk factors including young age, premenopausal status, presence of lymphovascular invasion (LVI), high tumor grade, or tumor size 2-5cm. Simultaneously, the evolution of our understanding of breast cancer biology has led us to better identify patients for whom the administration of systemic treatment prior to surgery reduces tumor load, not only in the case of locally advanced tumors but also for earlier stages, namely in the case of unfavorable molecular subtypes. The role of PMRT in the context of these patients treated with primary systemic therapy (PST), especially after a good tumor response, is under evaluation by various studies. This review identifies factors that may permit PMRT omission in a selected group of patients after PST.

Prediction of tumor response of rectal cancer cells via 3D cell culture and in vitro cytotoxicity assay before initiating preoperative chemoradiotherapy.

The aim of the present study was to investigate the utility of 3D cell culture and in vitro cytotoxicity assays, performed using cells derived from biopsies obtained prior to the initiation of preoperative chemoradiotherapy (preop-CRT), in predicting tumor response to chemoradiotherapy following preop-CRT in rectal cancer. Biopsies were obtained from 49 patients with locally advanced rectal cancer that underwent preop-CRT between August 2015 and March 2017. Tumor tissue was obtained before initiating preop-CRT. The response to chemoradiation was assessed by in vitro cytotoxicity assay following 3D cell culture and radiation treatment. The associations between the results from the cytotoxicity assay, and tumor regression grade (TRG) and yp node (ypN) positivity were investigated. Among 49 patients, 26 patients were available for analysis. Cytotoxicity ranged from 25.5-72.6% (median, 47.6%). There was no difference in cytotoxicity according to the TRGs 1-5 (P=0.940), or good tumor response (TRGs 1-2 vs. TRGs 3-5; P=0.729). However, there was a significant difference in cytotoxicity between the ypN-negative and -positive groups (53.2±14.1 and 38.7±10.1, respectively; P=0.021). Following dichotomization of patients with 45% cut-off value, the cytotoxicity assay was the only factor that predicted ypN positivity in multivariate analysis (odds ratio, 13; 95% confidence interval, 1.2-133.2; P=0.031). In conclusion, the cytotoxicity assay using the 3D cell culture method can be used to predict tumor response, particularly ypN positivity, in patients with rectal cancer who are scheduled for preop-CRT.

Radiofrequency Ablation for Lung Carcinomas: A Retrospective Review of a High-Risk Patient Population at a Community Hospital

Purpose: The purpose of this study is to retrospectively evaluate the technical efficacy, safety, and treatment outcomes of percutaneous radiofrequency ablation (RFA) of lung tumors in patients not amenable to surgery at an urban community hospital. Materials and Methods: Informed consent and IRB approval was obtained. Eligible tumors were defined as those in patients deemed poor surgical candidates by multidisciplinary consensus or those refusing surgery. Response to treatment was assessed by computed tomography (CT) performed immediately postprocedure and regular intervals up to 36 months later. Complete response was measured as a 30% decrease in mean tumor diameter without evidence of contrast enhancement or tumor growth within the ablation zone as defined by the response evaluation in solid tumors. Patient demographics, technical success, postprocedure complications, and survival were assessed and compared with data available in literature. Results: Twenty-four patients with a total of 29 tumors underwent percutaneous CT guided RFA for biopsy-proven lung malignancies between 2010 and 2016. Complete response was achieved in 82% (14/17) of treated tumors in patients who complied with postprocedure imaging recommendations. Immediate postprocedure complications occurred following 27.6% (8/29) ablations with pneumothorax being the most common, 17.2% (6/29). Mean survival is 28.5 months (95% confidence interval: 19.7–37.3). Progressive disease was seen in 18% (3/17) patients. No immediate treatment mortality was found. No significant difference was found in survival in patients with multiple comorbidities as measured by the Charlson Comorbidity Index. Conclusions: RFA of lung tumors is a well-tolerated procedure with low incidence of minor complications, a good tumor response and survival benefit in selected patients in the community setting. This is a positive endorsement of the potential success of tumor RFA programs outside of the academic setting. In addition, patients with multiple comorbidities should still be considered candidates for RFA as no difference was seen in survival in patients with multiple medical comorbidities.

Association Between Radiation Tolerance of Lymphocytes and Clinical Outcomes in Cervical Cancer.

This study evaluated whether the lymphocyte tolerance factor (LTF) was an indicator of radiation tolerance of lymphocytes (RTL) using the relative lymphocyte count (RLC), and considering clinical outcomes. A total of 92 cervical cancer patients treated with concurrent chemoradiotherapy (CCRT) were analysed. RLC0 was pre-treatment RLC, and RLC1, and RLC2 were at the first and second week of CCRT, respectively. LTF1 was RLC1:RLC2. LTF2 was the dimension of the convex or concave shape comprising the three RLC vertexes. Patients were divided into three groups: good RTL group, low LTF1; moderate RTL group, high LTF1 and low LTF2; and poor RTL group, high LTF1 and high LTF2. Patients with good tumour response to radiotherapy were mostly included in the good RTL group than in the other groups. The poor RTL group had lower 3-year progression-free survival (57.1% vs. 83.8% and 82%, p=0.01) and 5-year disease-specific survival (71.8% vs. 90.4% and 94.9%, p=0.062) rates than the moderate and good RTL groups. Multivariate analyses showed that poor RTL was a significant survival predictor. The poor RTL group according to LTF is a potential predictor of clinical outcome.

Nadir/pre-chemoradiotherapy ratio of white blood-cell count can predict tumor response and recurrence-free survival in locally advanced rectal cancer: a multi-institutional analysis

The objective of this study was to evaluate whether change of white blood-cell (WBC) count before and during chemoradiotherapy (CRT) might be associated with susceptibility to radiation and tumor response. Medical records of 641 patients with rectal cancer who received preoperative CRT followed by curative surgery were retrospectively reviewed in five tertiary centers. Complete blood cell with differential count was measured weekly during the period of CRT. We assessed nadir/pre-CRT ratio of WBC count as a predictor for tumor response to CRT and a prognostic factor for recurrence-free survival. Enrolled patients were divided into low WBC ratio (LWR) and high WBC ratio (HWR) arms with cut-off value of 0.49 calculated by receiver operating characteristic curve. Of 641 patients, 490 (76.4%) and 151 (23.6%) were categorized into HWR (> 0.49) arm and LWR (≤ 0.49) arms, respectively. Complete pathologic response rate after CRT was significantly higher in LWR arm than that in HWR arm (23.8% vs. 12.2%, p = 0.001). In logistic regression analysis, carcinoembryonic antigen (CEA) level over 5ng/ml [adjusted odds ratio (OR) 0.566, 95% confidence interval (CI) 0.351-0.912; p = 0.019) and HWR (adjusted OR 0.412, 95% CI 0.256-0.663; p = 0.001) were significantly negative factors of pathologic complete response. The 5-year recurrence-free survival rate was significantly higher in the LWR group than that in the HWR group (83.3% vs. 67.6%, p = 0.001). Low nadir/pre-chemoradiotherapy ratio during preoperative CRT can predict good tumor response. It is significantly associated with improved recurrence-free survival in rectal cancer.

Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in rectal cancer patients following neoadjuvant chemoradiotherapy.

There is uncertainty over the effect of systemic inflammatory response on oncologic outcomes in patients who underwent neoadjuvant chemoradiotherapy and surgery for rectal cancer. We investigated the association between neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as markers of systemic inflammation and tumor response and prognosis after treatment. A total of 176 patients who underwent neoadjuvant chemoradiotherapy and curative surgery for rectal cancer were analyzed retrospectively. Pretreatment hematologic parameters and the main clinical factors for patients and tumors were investigated with respect to their relationship with tumor regression and survival. In the receiver operating characteristic analysis, NLR 2.0 and PLR 133.4 had the highest sensitivity and specificity in predicting tumor response. NLR <2.0 and PLR <133.4 were significantly correlated with good tumor response (odds ratio [OR] 2.490, 95% confidence interval [CI] 1.264-4.904, p = .008; OR 3.009, 95% CI 1.477-6.127, p < .001). Patients with NLR <2.0 had significantly better 5-year disease-free survival rate and overall survival rate compared to patients with NLR ⩾2.0 in multivariate analysis (86.8% vs 70.7%, p = .014; 92.4% vs 71.9%, p = .027). Elevated NLR and PLR levels can be considered as predictors of poor pathologic response, and NLR can be considered a prognosticator in patients who underwent neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Characteristics and treatment of new-onset arthritis after checkpoint inhibitor therapy

Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (IRAEs). Characterisation and data on treatment of musculoskeletal IRAEs are scarce. In this cohort study, patients receiving ICI therapy who experienced...

Abstract CT087: Early tumor immune microenvironment (TME) modulation by the BRAF inhibitor (BRAFi) dabrafenib (D) and/or the MEK inhibitor (MEKi) trametinib (T) in patients (pts) with BRAF V600E/K-mutant melanoma in the COMBAT trial

Abstract Several trials are evaluating combinations of BRAFi/MEKi and immunotherapy (IO) treatment (Tx) in melanoma. This descriptive biomarker study explored tumor cell and TME modification during BRAFi, MEKi or combination Tx in pts with BRAF V600E/K–mutant unresectable or metastatic melanoma and their potential impact on biomarkers implicated in response to IO. 48 pts enrolled and were randomized 1:1:1 to receive D+T, D, or T (n = 16 each). In the D and T arms, pts received D+T after 8 wk of D or T alone. Tumor biopsies were collected at baseline (BL), wk 2, 8, and 10, and at disease progression. Phosphorylated ERK (pERK), PD-L1, CD8, and CD68 protein expression was analyzed by IHC. RNA expression was assessed by NanoString immune profiling of 770 genes covering adaptive, innate, and humoral immune responses. The primary objectives were to evaluate pERK reduction from BL and characterize safety and efficacy in each Tx arm with changes in pERK H-score. At the final data cutoff, 21 pts (44%) completed the study, including 3 deaths and disease progression. Across Tx arms serious adverse events were reported in 19 pts (40%); no new safety signals were observed. In the biomarker population (pts with BL and ≥ 1 on-Tx biopsy; n = 42), the number of evaluable samples decreased with time due to insufficient tumor material (often due to good tumor response). Due to this limitation, the correlation between biomarker changes and clinical response could not be analyzed, but early biomarker changes are reported. pERK H-score, a MAPK pathway activity marker, decreased from BL to wk 2 in 13 of 17 pts (D, 4/5 pts; T, 6/7 pts; D+T, 3/5 pts) and from BL to wk 8 in 5 of 8 pts (D, 2/3 pts; T, 2/3 pts; D+T, 1/2 pts). IHC showed an early increase in CD8+ and CD68+ cells in the center of tumors compared with the periphery in all 3 arms. Innate immune response, chemotaxis, MHC class II antigen presentation, and complement pathway genes were upregulated. RNA expression of PD-L1, IFNγ pathway genes, and immunosuppressive cytokines IL-6 and CCL2 were slightly increased. Intriguingly, both M1 (IRF5) and M2 (CD163) macrophage genes were upregulated, with an increase of protumoral cytokines (eg, VEGF, TNF) and the MDSC-related cytokine CSF-1. These results indicate that D and T, alone or combined, induced early modification of the melanoma TME, with a tendency to recruit cytotoxic CD8+ cells and increase antigen presentation, which may, however, be offset by induction of immunosuppressive events. Early induction of complement pathways is a novel finding that needs further investigation as it can be both cytotoxic and cytoprotective for tumor cells. These findings provide additional rationale for evaluation of IO and/or agents targeting MDSC following or combined with BRAFi/MEKi in BRAF-mutant melanoma. Additional efficacy and safety analyses will be presented. Citation Format: Caroline Robert, Shensi Shen, Delphine Allard, Ana Arance Fernández, Caroline Dutriaux, Egbert de Jong, Matthew Squires, Jean-Jacques Grob. Early tumor immune microenvironment (TME) modulation by the BRAF inhibitor (BRAFi) dabrafenib (D) and/or the MEK inhibitor (MEKi) trametinib (T) in patients (pts) with BRAF V600E/K-mutant melanoma in the COMBAT trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT087.

An Extended Hypofractionated Palliative Radiotherapy Regimen for Head and Neck Carcinomas.

Palliative radiotherapy to patients with head and neck cancer is often necessary, but there is a substantial variation in the treatment regimens reported in the literature, and consensus on the most appropriate schedules does not exist. In order to minimize acute toxicity while at the same time trying to achieve prolonged tumor control, a long hypofractionated regimen has been used routinely in Denmark. In the current retrospective study, we investigated the outcome in patients intended for palliative radiotherapy with this regimen. Patients with newly diagnosed head and neck cancer treated with palliative radiotherapy of 52-56 Gy in 13-14 fractions twice weekly from 2009 to 2014 were included. Patients were excluded if they had previously received radiotherapy. Data on disease location, stage, patient performance status (PS), treatment response, acute skin and mucosal toxicity, and late fibrosis were collected prospectively and supplemented with information from medical records. 77 patients were included in the study. Fifty-eight patients (75%) completed the intended treatment. Loco-regional tumor response (complete or partial) was evaluated 2 months posttreatment and observed in 45% of the entire population corresponding to 71% of patients alive. PS had a significant influence on survival (p = 0.007) and on not completing the intended treatment. Grade III or IV acute mucositis were observed in 25%, and grade III or IV acute dermatitis observed in 15%. Palliative hypofractionated radiotherapy with 52-56 Gy in 13-14 fractions shows good tumor response and tolerability in a vulnerable patient population. However, it may not be suited for patients in poor PS.

Prognostic role of neutrophil‐to‐lymphocyte ratio on esophageal cancer patients who received definitive chemoradiotherapy

AbstractObjectiveThe neutrophil‐to‐lymphocyte ratio (NLR), a simple biomarker that can reflect the host antitumor immune response, has been associated with patient prognosis in several solid tumors. The aim of the present study was to evaluate the ability of NLR to predict clinical tumor response and prognosis in patients with locally advanced esophageal squamous cell carcinoma who received definitive chemoradiotherapy.MethodsA total of 147 patients with advanced esophageal squamous cell carcinoma treated at Shandong Cancer Hospital Affiliated with Shandong University, Jinan, China, between January 1, 2012 and December 31, 2013 were retrospectively recruited for analysis. The patients were divided into a low NLR group (NLR ≤2.46, n = 74) and a high NLR group (NLR &gt;2.46, n = 73) according to pretreatment NLR. The predictive value of NLR for clinical tumor response and prognosis was examined.ResultsCompared with their matched counterparts, patients in the low NLR group showed a good clinical tumor response (P &lt; 0.001). The NLR before chemoradiotherapy was significantly lower in patients who achieved complete response than in patients who did not achieve complete response (2.2 ± 0.9 vs. 2.7 ± 1.1, P = 0.024). Logistic regression analysis revealed that pretreatment NLR was negatively correlated with tumor response (odds ratio 0.60, 95% confidence interval 0.43–0.84; P = 0.003). In the univariate analysis, cT stage status (PPFS = 0.001; POS = 0.007), tumor response (PPFS &lt; 0.001; POS &lt; 0.001) and NLR (PPFS = 0.005; POS = 0.008) were significantly associated with PFS and OS. The Cox proportional hazards model showed that tumor response (PPFS = 0.002; POS = 0.003) and NLR (PPFS = 0.021; POS = 0.017) were independent predictors of prognosis.ConclusionsIn patients with esophageal squamous cell carcinoma, NLR can be used as a simple marker to predict clinical tumor response and prognosis.

MRI-based EMVI positivity predicts systemic recurrence in rectal cancer patients with a good tumor response to chemoradiotherapy followed by surgery.

This study aimed to determine the prognostic value of baseline magnetic resonance imaging-based extramural vascular invasion status (EMVI) among rectal cancer patients with a good tumor response to standard chemoradiotherapy followed by surgery. A total of 359 patients with ypT0-2/N0 disease from The Yonsei Multicenter Colorectal Cancer Electronic Database were retrospectively included between January 2000 and December 2014. Magnetic resonance images and medical records were reviewed to investigate risk factors for tumor recurrence. When we compared patients without and with EMVI, significant differences were observed in the 5-year disease-free survival rate (DFS) (80.8% vs 57.8%, P = 0.005) and in the 5-year systemic recurrence-free survival rate (SRFS) (86.9% vs 64.3%, P = 0.007). In the multivariate analysis, both mrEMVI and APR independently predicted overall DFS (APR; HR 2.088, 95% CI: 1.082-4.031, P = 0.028, mrEMVI; HR: 2.729, 95% CI: 1.230-6.058, P = 0.014). mrEMVI was only independent prognostic factor for systemic recurrence with statistical significance (HR: 3.321, 95% CI: 1.185-9.309, P = 0.022). Even in rectal cancer patients with a good response to chemoradiotherapy followed by curative surgery, extramural vascular invasion and APR may predict poor disease-free survival outcomes. Intensified treatment strategy should be considered.

Evaluation of clinical and endoscopic toxicity after external beam radiotherapy and endorectal brachytherapy in elderly patients with rectal cancer treated in the HERBERT study

IntroductionThe HERBERT study evaluated a high-dose-rate endorectal brachytherapy boost (HDREBT) after EBRT in medically inoperable/elderly patients with rectal cancer. The response-rates are promising but not without risk of toxicity. The current analysis provides a comprehensive overview of patient reported, physician reported and endoscopically observed toxicity. Material and methodsA brachytherapy dose finding study was performed in 38 inoperable/elderly patients with T2-T4N0-1 rectal cancer. Patients received EBRT (13 × 3 Gy) followed by three weekly HDREBT applications (5–8 Gy). Toxicity was assessed via three methods: patient and physician (CTCAEv3) reported rectal symptoms and endoscopically. Wilcoxon’s signed rank test, paired t-test and Spearman’s correlation were used. ResultsPatient reported bowel symptoms showed a marked increase at the end of EBRT and two weeks after HDREBT. Acute grade 2 and 3 proctitis occurred in 68.4% and 13.2% respectively while late grade 2 and ≥3 proctitis occurred in 48% and 40%. Endoscopic evaluation mainly showed erythema and telangiectasia. In three patients frank haemorrhage or ulceration occurred. Most severe toxicity was observed 12–18 months after treatment. ConclusionFor elderly patients with rectal cancer, definitive radiotherapy can provide good tumour response but has a substantial risk of toxicity. The potential benefit and risks of a HDREBT boost above EBRT alone must be further evaluated.

The prechemoradiotherapy/nadir ratio of white blood-cell count to predict tumor response and survival in locally advanced rectal cancer.

783 Background: Predicting treatment response of preoperative chemoradiotherapy (CRT) in patients with rectal cancer is important for physicians to guide a patient to the relevant treatment. We evaluate the change of white blood cell (WBC) count before and during CRT if it is associated with susceptibility to the CRT and affects tumor response. Methods: Medical records of 641 patients with rectal cancer who received preoperative CRT followed by curative surgery were retrospectively reviewed. Complete blood cell counts were measured weekly before and during the radiation therapy. We assessed the pre-CRT/nadir ratio of WBC count for the treatment response to CRT and recurrence-free survival. Results: The enrolled patients were divided into two groups of high WBC ratio (HWR) and low WBC ratio (LWR) with the cutoff value of 0.49, which was found by receiver operating characteristic curve (Sensitivity, 0.38 and 1-Specificity, 0.22; p=0.007). In 641 patients, 490 (76.4%) were HWR group and 151 (23.6%) were LWR group. Complete pathologic response rates were 12.2% in HWR group and 23.8% in LWR group, respectively (p=0.001). Downstaging rates of each group were 37.8% and 48.3%, respectively (p=0.02). In the logistic regression analysis, CEA level over 5ng/ml (Adjusted OR 0.566, 95% CI 0.351-0.912; p=0.019) and HWR (Adjusted OR 0.412, 95% CI 0.256-0.663; p=0.001) were significant adverse factors of the pathologic complete response. The 5-year recurrence-free survival rate was significantly higher in LWR group than in HWR group (67.6% and 83.3%; p=0.001). Conclusions: Low WBC ratio predicts a good tumor response to the preoperative CRT, and is significantly associated with an improved recurrence-free survival in rectal cancer.

Predictors of sensitivity to preoperative chemoradiotherapy of rectal adenocarcinoma.

The purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma. Ninety-eight patients with nonmetastatic rectal adenocarcinoma received preoperative concurrent chemoradiotherapy and underwent mesorectal excision. After treatment, tumor response according to tumor regression grade were evaluated. The correlation of clinicopathologic factors to tumor response was analyzed. The results from a univariate analysis indicated that pretreatment carcinoembryonic antigen level ≤3.0 ng/ml (P = 0.002), non-fixed tumor (P = 0.001), and tumor circumferential extent ≤50% (P = 0.001) were associated significantly with a good tumor response. They also indicated that pretreatment positive lymph nodes (P = 0.032) were associated significantly with a poor tumor response. In multivariate analysis, the results indicated that pretreatment carcinoembryonic antigen level (hazard ratio, 2.930; P = 0.003), tumor mobility (hazard ratio, 2.651; P = 0.002) and circumferential extent of tumor (hazard ratio, 2.394; P = 0.019) independently predicted a good pathologic response rate. Pretreatment positive lymph nodes were not significantly associated with a good response (hazard ratio, 0.361; P = 0.191). Pretreatment carcinoembryonic antigen level, tumor mobility and circumferential extent of tumor may be helpful in predicting responsiveness in rectal adenocarcinoma to preoperative chemoradiotherapy, although the results should be confirmed in larger, more homogeneous studies.

Comparative Evaluation of Palliative Radiotherapy with Chemotherapy vs. Palliative Radiotherapy Alone in Locally Advanced Head and Neck Cancer

Background: The aim of the study was to evaluate and compare the efficacy, tolerability and toxicity of two palliative radiotherapy (RT) schedules in locally advanced head and neck carcinoma (LAHNC), i.e., Quad Shot schedule with chemotherapy and Quad Shot schedule alone. Methods: The patients were randomly divided into two groups of 30 each. Group I patients were planned for 14.8 Gy in 4 fractions over 2 days every 3 weeks for three cycles. All these patients also received paclitaxel 60 mg/m2 intravenous. Group II patients received 14.8 Gy in 4 fractions over 2 days every 3 weeks for three cycles alone. All these patients in Group I and II received total radiation dose of 44.4 Gy. Results: At the end of treatment, complete tumor response (CR) in Group I was better than Group II (40% vs. 36.7%). Disease status (tumor+node) at the end of treatment in terms of complete response was 36.7% vs. 0% (11/30 and 0/30) in Group I and II. Disease status at 6 months of follow up was noted as follows: complete tumor response in Group I and II was 23.3% (7/30) vs. 10% (3/30) (p=0.012). Complete nodal response was 35.7% (10/28) in Group I and 6.67% (02/30) in Group II (p= 0.538). Overall, no evidence of disease was observed in 16.7% (5/30) in Group I and 3.3% (1/30) in Group II respectively (p<0.001). Conclusion: This palliative schedule has been shown to provide good tumor response and palliation of symptoms. The toxicity profile remains low with the addition of paclitaxel. Further investigation is warranted in a larger trial. Palliation of symptoms resulted in improved quality of life for these group of patients

Exceptional Response to Vemurafenib and Cobimetinib in Anaplastic Thyroid Cancer 40 Years After Treatment for Papillary Thyroid Cancer

Case description: We present an unusual case of a patient that developed anaplastic thyroid cancer 40 years after treatment for papillary thyroid cancer. The patient presented with locoregional recurrence and distant metastasis. Tumor genotyping identified a BRAF V600E mutation. The patient was treated with drugs targeting BRAF V600E and MEK (vemurafenib and cobimetinib, respectively). The patient had a remarkable response with the right neck tumor shrinking 81% in size and disappearance of the distant metastases over an 8-month period. The patient underwent surgical resection of the residual tumor with genetic testing of the specimen showing persistent BRAF V600E mutation population of cells. Conclusion: Targeted drug therapy has been used with discretion on a case-by-case basis for anaplastic thyroid cancer and may result in good tumor response.

Reirradiation on recurrent cervical cancer case: Treatment response and side effects

Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was also no correlation between tumor response and tumor size of ≤4 cm vs. > 4 cm.

Chemoembolization Adopting Polyethylene Glycol Drug-Eluting Embolics Loaded With Doxorubicin for the Treatment of Hepatocellular Carcinoma.

The purpose of this study is to determine the efficacy and tolerability of transarterial chemoembolization (TACE) using polyethylene glycol (PEG) drug-elutable microspheres loaded with doxorubicin for treatment of hepatocellular carcinoma (HCC). Forty-two patients with unresectable HCC, as determined by a tumor board, were assigned to undergo TACE and were treated with PEG drug-elutable embolics loaded with doxorubicin. Patients were prospectively enrolled and included 32 (76%) men and 10 (24%) women. Their median age was 65 years (range, 42-83 years). Patients were treated with 50 mg of doxorubicin loaded in 2 mL of PEG embolics (mean [± SD] diameter, 100 ± 25 µm) that were infused via a chemoembolization method. Data collected included previous cancer therapy, tumor size, number of lesions, history of TACE, tumor response (at 1, 3, and 6 months), type and intensity of adverse events, and quality of life (QOL) analysis. One month after TACE, the overall tumor response rate was 79% (50% complete response, 29% partial response, 17% stable disease, and 5% progressive disease). At 3 months, the rates were 48% for complete response, 24% for partial response, 24% for stable disease, and 3% for progressive disease. At 6 months, the rates were 43% for complete response, 19% for partial response, 29% for stable disease, and 10% for progressive disease. TACE was well tolerated by all patients, with no evidence of procedure-related complications or systemic drug-related adverse events. Fever (33%), increase in transaminase level (17%), and pain (33%) were the most frequent adverse events, and their intensity was mostly mild (grades 1 and 2). The QOL scores were 80 at 1 month, 81 at 3 months, and 82 at 6 months after TACE. These data suggest that PEG embolics are efficacious and safe for the treatment of HCC, as indicated by their good tolerability, QOL scores, and high tumor response.