Completion Of Neoadjuvant Treatment Research Articles

Pathological complete response of locally advanced triple-negative breast cancer: case report

Background. Triple-negative breast cancer is the most aggressive molecular subtype among breast malignancies. Due to the high proliferative activity of tumor cells and the lack of targets for targeted therapy, neoadjuvant chemotherapy plays the main role in complex treatment of this subtype. The optimal time to start neoadjuvant chemotherapy is defined as less than 8 weeks. Delays in time to treatment initiation may adversely affect treatment outcomes, as well as cause local or systemic disease progression. Achieving complete pathological response after neoadjuvant chemotherapy reduces the relative risk of relapse by more than 70 %, which, in turn, leads to a significant improvement in long-term survival of these patients. Description of the clinical case. A 32-year-old woman came to the clinic 15 months after being diagnosed with triple-negative breast cancer. The patient was treated with alternative medicine methods for 15 months, and upon admission to the hospital, the patient had pronounced local tumor growth with massive decay, tumor lysis syndrome and nutritional disorders. We decided to perform neoadjuvant chemotherapy: 12 cycles of weekly paclitaxel + carboplatin, followed by 4 cycles of dose-dense doxorubicin + cyclophosphamide. Chemotherapy resulted in a significant reduction in tumor size and improvement of health status of the patient. There were no clinically significant side effects requiring hospitalization or dose reduction. Upon completion of neoadjuvant treatment, the patient underwent mastectomy. The histological examination revealed a complete pathological response of the primary tumor and regional lymph nodes. The patient underwent adjuvant external beam radiation therapy. The patient is alive 3 years after diagnosis and 1.5 years after treatment completion. She plans delayed breast reconstruction with contralateral breast augmentation. Conclusion. This is a rare case of locally advanced triple-negative breast cancer with pathological complete response to neoadjuvant chemotherapy 15 months after diagnosis.

Evaluating gut microbiome as a biomarker of pathological complete response in patients with early locally advanced triple negative breast cancer (LA TNBC): A pilot study.

593 Background: It has previously been shown that microbial metabolic pathways are differentially activated in immunotherapy resistance, hence can serve as potential biomarker as well as target for therapeutic intervention. With the advent of Immune Checkpoint Blockers (ICB) in the neoadjuvant (NA) setting of locally advanced (LA) TNBC, we hypothesized that similar microbial metabolite mediated resistance may be at play. We are presenting data demonstrating differences in microbiome and metabolites in these patients. Methods: 28 patients who received NA pembrolizumab and chemotherapyfor LA TNBC were identified at Moffitt Cancer Center and Tampa General Hospital between February 2022 to October 2023. Blood and stool samples were collected at therapy initiation, at completion of neoadjuvant treatment and/or when the patients developed grade 3 or higher toxicity to therapy. We evaluated stool metagenomics and untargeted stool/plasma metabolomics as correlatives. Patient characteristics were as follows: 21 Caucasian, 3 African-American, 2 Hispanic, 2 unknown, median age 51 years, median body mass index (BMI) 28.5 kg/m2. 17 patients had stage II, while 11 patients had stage III TNBC. Results: Response was assessed in 27 patients, of which 11 had pCR (ypT0/is ypN0) while 16 had residual disease (RD). 1 patient progressed, while on NA therapy, while 8 patients developed grade 3-4 immune related adverse events leading to treatment discontinuation and death in one patient. We conducted shallow shotgun metagenomic sequencing and untargeted metabolomic profiling on pre and post treatment fecal and plasma samples respectively to identify gut microbial diversity, composition and differentially abundant metabolites associated with pCR.There wasno difference in alpha and beta diversity; however significant enrichment of microbiota with genus Akkermansia HR 0.04, p 0.03 was noted in those with pCR. We observed higher abundance of tryptophan metabolizing clostridium species HR 50541, p <0.001, along with differential activation of microbial tryptophan pathway in those with residual disease, specifically higher abundance of hydroxyindole acetic acid HR 1.54 P<0.005, indole propionic acid HR 1.75 p 0.05 and indole butyric acid HR 1.86 p 0.04. Conclusions: To our knowledge this is the first analysis of differences in the microbiome and microbial metabolism in patients with LA TNBC treated with NA ICB. Despite being a small study, it shows a more aggressive disease pattern with higher RD than noted in KEYNOTE 522 and shows significant concern for serious immune mediated adverse effects. This highlights the importance of biomarkers to stratify patients most likely to benefit from ICB. Enrichment of microbiota and immunosuppressive tryptophan metabolites were associated with pCR and should be validated in large studies as biomarker of response to NA ICB in TNBC.

A prospective phase 2 single-arm study to evaluate the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy in patients with locally advanced esophageal squamous cell carcinoma (Keypoint-1).

4088 Background: Esophageal squamous cell carcinoma (ESCC) is the most prevalent esophageal cancer type worldwide with poor prognosis and limited treatment options. Combination immunotherapy and chemotherapy improved the outcomes in patients (pts) with metastatic esophageal cancer. However, the benefit of neoadjuvant immuno-chemotherapy in pts with locally advanced ESCC is unknown. We evaluated the efficacy and safety of neoadjuvant treatment with pembrolizumab plus chemotherapy in pts with locally advanced ESCC. Methods: Eligible pts who were aged 18-80 years with untreated, locally advanced ESCC were enrolled in this single-arm, phase 2 trial at Peking Union Medical College Hospital (China) from July 2020 to April 2022. Pts received neoadjuvant treatment with docetaxel 75 mg/m2, carboplatin area under the curve (AUC) 4-5 (or cisplatin 75 mg/m2), and pembrolizumab 200 mg via IV every 3 weeks. Within 4-8 weeks of completion of neoadjuvant treatment, pts underwent surgery. The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints were treatment-related adverse events and R0 resection rate. The study is registered at ClinicalTrials.gov (NCT05302011). Results: Thirty pts were enrolled (Table). As of December 1, 2023, median follow-up time was 27.9 months. Twenty-eight pts received 4 cycles and 2 received 3 cycles of the neoadjuvant treatment. Six pts did not proceed with surgery because of disease progression (3/6) and personal choice (3/6). Twenty-four pts (24/30, 80%) underwent minimally invasive esophagectomy (MIE). The R0 resection rate was 100%. Perioperative complications were manageable, including anastomotic leakage (2/24, 8.3%) and nerve injury (1/24, 4.2%). Of these 24 pts, 7 (29.2%) achieved pCR and 5 (20.8%) were CAP1 (near complete response, College of American Pathologists protocol). The median disease-free survival (DFS) was 30.6 months. Median overall survival data is not yet available. Grade 3/4 treatment-related adverse events include leukopenia (10, 33.3%), alopecia (3, 10.0%), and pneumonitis (1, 3.3%). One patient died of Stevens-Johnson syndrome. We are conducting molecular and immunological correlative studies to explore potential biomarkers related to the treatment. Conclusions: Neoadjuvant treatment with combination pembrolizumab and chemotherapy demonstrated encouraging anti-tumor activities, good surgical outcomes and a manageable safety profile in pts with locally advanced ESCC, supporting further evaluation in a prospective randomized phase 3 trial. Clinical trial information: NCT05302011 . [Table: see text]

Assessment of breast cancer optimal care timeframes in a regional and rural real-world setting: A regional cancer centre experience in Australia.

e12614 Background: The Breast Cancer Optimal Care Pathway (Cancer Australia) is a national patient-centred guideline that seeks to standardise the management pathway for breast cancer patients and spans from early diagnosis through to survivorship. The guideline provides suggested optimal management-based timeframes including the time from general practitioner (GP) referral to specialist review (<2 weeks), time from specialist review to completion of investigations and multidisciplinary discussion (MDT) (<2 weeks), time to initiation of neoadjuvant therapy from MDT (<4 weeks) and time to surgery following completion of neoadjuvant therapy (<6 weeks). Methods: Retrospective data was obtained for patients undergoing neoadjuvant systemic therapy for newly diagnosed breast cancer between 2021 and 2023 at a regional tertiary cancer centre in Australia (Townsville University Hospital). Data included baseline patient demographics, tumour characteristics, staging, key optimal care pathway timepoints, treatment regimen and outcomes. Median and interquartile range were calculated for key timepoints. Results: Overall, 53 patients (100% female) were identified for inclusion. 10% of patients identified as Indigenous (n=5), 36% lived rurally (n=19) and 13% were treated using a tele-chemotherapy model (n=7). Receptor status was triple-negative in 20 patients (38%), hormone-positive in 17 patients (32%) and HER2-positive in 16 patients (30%). 15% of patients had stage I disease (n=8), 58% had stage II disease (n=31), 21% had stage III disease (n=11), while 6% of patients had oligometastatic stage IV disease at diagnosis (n=3). 24 patients (50%) were seen by a specialist within 2 weeks of GP referral (median: 15 days; IQR 9-19). 46 patients (87%) had a definitive management plan formulated at MDT within 2 weeks of specialist review (median: 5 days; IQR 4-9), with delays most commonly due to pending investigations (n=5; 9%). 48 patients (91%) proceeded with neoadjuvant therapy within 4 weeks of MDT (median: 14 days; IQR 11-22), with delays most commonly due to concurrent infections including COVID. 90% of patients (n=46) were ultimately commenced on neoadjuvant treatment within the 8-week optimal care timeframe from initial GP referral (median: 34 days; IQR 27-47). In comparison to patients living locally, patients residing in rural areas were less likely to achieve this target (79% v 97%, p=0.05). 83% of patients (n=43) underwent surgery within 6-weeks of completion of neoadjuvant treatment (median: 30 days; IQR 27-34). Conclusions: The neoadjuvant breast cancer optimal care timeframes were feasible to achieve in a regional and rural setting. However, further targeted research is needed to improve adherence to optimal care standards for patients from rural areas, such as the timeframe from initial referral to completion of investigations and MDT.

Abstract PS05-07: Early prediction of response to Neoadjuvant Immunotherapy in Triple Negative Breast Cancer (TNBC) with DCE-MRI

Abstract Purpose: Neoadjuvant immunotherapy (NIT) in combination with neoadjuvant chemotherapy (NCT) was recently approved for treatment of TNBC patients with increased rates of pathologic complete response (pCR) compared to NCT alone. The aim of this study was to evaluate if dynamic contrast-enhanced (DCE)-MRI performed after 2 and/or 4 cycles of NIT + NCT, can predict which patients will achieve pCR, potentially triaging them to continuation of NIT+NCT or, when appropriate, to de-escalation trials. Alternatively, identified chemoresistant tumors who are unlikely to achieve pCR may be directed to other treatment strategies, including novel targeted trials, and avoid the unnecessary toxicity of NIT. Methods and Materials: Preliminary analysis included 64 patients from prospective IRB-approved study (NCT02276443) with stage I-III TNBC who underwent DCE-MRI at baseline (BL), after 2 cycles (C2), and 4 cycles (C4) of NIT combined with standard of care NCT (Paclitaxel +/- carboplatin). Tumor volumes were calculated using 3 axis measurements of the index lesion at the DCE MRI and percent tumor volume reduction (TVR) between BL, C2, and C4 was calculated. pCR was assessed at surgery after completion of neoadjuvant treatment. Correlation between pCR and TVR was evaluated using ROC analysis. Results: 59% (38/64) of TNBC patients achieved pCR after NIT+NCT. DCE-MRI after 2 cycles of NIT+NCT was able to predict pCR with an AUC of 0.71 (95% CI: 0.57-0.84). TVR >90% at C2 predicted pCR with PPV 86%, and TVR < 35% predicted chemoresistance with NPV 100%. Following 4 cycles of treatment DCE-MRI was able to predict pCR with an AUC of 0.81 (95% CI: 0.69-0.92). TVR >95% at C4 was predictive of chemosensitivity with PPV 82%, while TVR < 75% was predictive of chemoresistance with NPV 100%. Conclusions: DCE-MRI volumetric changes early during NIT + NCT were able to predict pCR status of TNBC patients as either excellent responders or nonresponders, triaging them to SOC neoadjuvant therapy with option for de-escalation trials, or targeted therapies, respectively. These preliminary results will be validated in the larger cohort after completion of the ongoing prospective clinical trial. Citation Format: Gaiane Rauch, Mary Guirguis, Miral Patel, Rosalind Candelaria, Rania Mohamed, Tanya Moseley, H. T. Carisa Le-Petross, Jessica Leung, Gary Whitman, Deanna Lane, Marion Scoggins, Frances Perez, Jia Sun, Sanaz Pashapoor, Zhan Xu, Jason White, Peng Wei, Brandy Reed, Jong Bum Son, Ken-Pin Hwang, Bikash Panthi, Anil Korkut, Lei Huo, Kelly Hunt, Alyson Clayborn, Jennifer Litton, Vicente Valero, Debu Tripathy, Clinton Yam, Wei Yang, Jingfei Ma, Beatriz Adrada. Early prediction of response to Neoadjuvant Immunotherapy in Triple Negative Breast Cancer (TNBC) with DCE-MRI [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-07.

Abstract PO1-28-07: Neoadjuvant docetaxel plus cisplatin versus docetaxel plus doxorubicin and cyclophosphamide in early-stage triple-negative breast cancer (HNBC-001): results from a multicenter, randomized controlled, open-label phase II trial

Abstract Background: Adding platinum to anthracycline- and taxane-based neoadjuvant chemotherapy has improved pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC). However, the efficacy of combining docetaxel and platinum without anthracycline remains controversial. Methods: The HNBC-001 trial was a randomized, phase 2 controlled, and open-label investigation carried out in China at 6 hospitals. The participants who were aged 18–70 years, were histologically confirmed for TNBC clinical stage II–III, suitable for potentially curative surgery, and had an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 were selected for this trial. Participants were randomly categorized into two equal groups; those who received docetaxel plus cisplatin (75 mg/m2, respectively) and those who received docetaxel plus doxorubicin and cyclophosphamide (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2). These regimens were given every 3 weeks for 6 cycles. Randomization was stratified by tumor size and nodal status. The primary endpoint was the number of individuals achieving a pCR (ypT0/is ypN0). The trial was registered with chictr.org (number ChiCTR-1800019501). Results: Between November 28, 2018, and June 11, 2022, 212 patients were selected (n=106/treatment). The number of individuals who achieved pCR after docetaxel plus cisplatin treatment was 51.9%, and that of those who attained pCR after docetaxel plus doxorubicin and cyclophosphamide was 35.8% (P=0.019). After 21 months of median follow-up [interquartile range (IQR), 13 to 33], 11 of 106 patients (10.4%) in the docetaxel plus cisplatin group and 14 of 106 patients (13.2%) in the docetaxel plus doxorubicin and cyclophosphamide group had event-free survival (EFS) events [95% confidence interval (CI) =0.360 to 1.783, hazard ratio (HR) =0.801, P=0.585]. The incidence of grade 3 or 4 events was similar in both groups [57 (54%) vs. 51 (48%)]. However, no treatment-associated deaths were identified. Conclusions: In stage II to III TNBC, the docetaxel plus cisplatin regimen achieved higher pCR rates than docetaxel plus doxorubicin and cyclophosphamide, with a manageable toxicity profile. Consistent with the literature, the docetaxel plus cisplatin regimen demonstrated a favorable risk-to-benefit profile and could serve as an optimal neoadjuvant chemotherapy option for patients with high-risk TNBC. table 1: Patient characteristics figure 1: Study endpoints Error bars denote 95% CIs based on normal approximation. p values were calculated from the Chi-square test. (A) Frequency of patients who achieved a pathological complete response per treatment group (primary endpoint). (B) Frequency of patients who achieved a clinical breast tumour response per treatment group, assessed by serial MRI scans after completion of neoadjuvant treatment. (C) Frequency of patients who achieved a minimal residual disease (residual cancer burden class 0 or 1). (D) Frequency of patients who received breast-conservation surgery. table 2: Treatment-emergent adverse events Citation Format: Dechuang Jiao, Jianghua Qiao, Chengzheng Wang, Juntao Li, Xianfu Sun, Zhenduo Lu, Chongjian Zhang, Lianfang Li, Min Yan, Yueqing Feng, Yong Zhou, Miao Deng, Xinlan Liu, Mingde Ma, Haiquan Jia, Qingxin Xia, Xiuchun Chen, Zhenzhen Liu. Neoadjuvant docetaxel plus cisplatin versus docetaxel plus doxorubicin and cyclophosphamide in early-stage triple-negative breast cancer (HNBC-001): results from a multicenter, randomized controlled, open-label phase II trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-07.

Abstract PO5-16-05: Integrating Circulating Tumor Cells (CTCs) and Cell-free DNA (cfDNA) Signatures for Monitoring Treatment Response in Stage III/IV Inflammatory Breast Cancer

Abstract Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, comprising only between 1-5% of all breast cancer cases in the United States. Despite its low incidence, IBC accounts for 10% of breast cancer-related deaths and is often diagnosed with metastasis, resulting in shorter survival compared to non-IBC cases. The 5-year relative survival rate for all stages of IBC is 39%, dropping to 19% for patients with distant metastasis. Liquid biopsy-based biomarkers have emerged as potential analytes for predicting prognosis and monitoring response to therapies in IBC patients. We explored the prognostic role of liquid biopsy encompassing both CTCs and cfDNA in the blood of patients with stage III/IV IBC and their clinical outcomes. Methods: CTC and cfDNA analysis was performed on 90 blood samples from 47 patients with stage III and IV IBC. Samples were collected before (pre-treatment, n=43) initiation and after (post-treatment, n=47) completion of neoadjuvant chemotherapy. CTCs were enriched and enumerated using the CellSearch® platform (Menarini-Silicon Biosystems). CfDNA was extracted from plasma using MagMax™ Cell-Free Total Nucleic Acid Isolation Kit (Applied Biosystems™) and quantified using the Qubit™ dsDNA High Sensitivity kit (Invitrogen™). Differences in cfDNA concentrations were used to plot a receiver operating characteristic (ROC) curve which was then used to determine Area Under the Curve (AUC) and a cfDNA cut-off point. ROC cut-off was calculated based on Youden Index J. Survival analysis was performed by the Kaplan-Meier estimator and Cox regression models. P-values were measured using the Student t-test. Results: Prior to neoadjuvant treatment, CTC was detected in 51% of patient samples, and the median cfDNA concentration was 5.87 ng/mL (range 0.95-24.11 ng/mL). After completion of neoadjuvant treatment, CTC was detected in 25% of patient samples, and the median cfDNA concentration was 11.19 ng/mL (range 3.41-88.13 ng/mL). The cut-off points determined for pre-treatment and post-treatment cfDNA concentration was >4.2 ng/mL and >9.5 ng/mL respectively. At pre-treatment, CTC detection and cfDNA concentration >4.2 ng/mL were independently associated with disease relapse (P=0.007, 0.016, respectively). The combination of CTC detection and cfDNA concentration >4.2 ng/mL was significantly associated with disease relapse (P=0.0004), decreased relapse free survival (RFS, P=0.005) and overall survival (OS, P=0.007). At the post-neoadjuvant treatment time point, the combination of CTC detection and cfDNA concentration >9.5 ng/mL was significantly associated with relapse regardless of pCR status (P=0.02). Conclusion: The combined presence of CTCs and elevated cfDNA concentrations in patients with stage III/IV IBC after completion of neoadjuvant chemotherapy was associated with disease relapse regardless of pCR status. A combination of elevated cfDNA and CTC detection signatures after completion of neoadjuvant chemotherapy may be useful for risk stratification and adjuvant systemic therapy planning. Citation Format: Sridevi Addanki, Salyna Meas, Vanessa Sarli, Abdulkader Almosa, Wendy Woodward, Dhruvajyoti Roy, Anthony Lucci. Integrating Circulating Tumor Cells (CTCs) and Cell-free DNA (cfDNA) Signatures for Monitoring Treatment Response in Stage III/IV Inflammatory Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-05.

Complete Primary Pathological Response Following Neoadjuvant Treatment and Radical Resection for Pancreatic Ductal Adenocarcinoma.

Neoadjuvant treatment (NAT) for borderline (BD) or locally advanced (LA) primary pancreatic cancer (PDAC) is now a widely adopted approach. We present a case series of patients who have achieved a complete pathological response of the primary tumour on final histology following neoadjuvant chemotherapy +/- chemoradiation and radical surgery. Patients who underwent radical pancreatic resection following neoadjuvant treatment between March 2006 and March 2023 at a single institution were identified by retrospective case note review of a prospectively maintained database. Ten patients were identified to have a complete primary pathological response (ypT0) on postoperative histology. Before treatment, five patients were considered BD and five were LA according to National Comprehensive Cancer Network guidelines. All patients underwent staging Computed Tomography (CT) and nine underwent 18Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET/CT) imaging, with a mean maximum standardized uptake value (SUVmax) of the primary lesion at 6.14 ± 1.98 units. All patients received neoadjuvant chemotherapy, and eight received further chemoradiotherapy prior to resection. Mean pre- and post-neoadjuvant treatment serum Ca19-9 was 148.0 ± 146.3 IU/L and 18.0 ± 18.7 IU/L, respectively (p = 0.01). The mean duration of NAT was 5.6 ± 1.7 months. The mean time from completion of NAT to surgery was 13.1 ± 8.3 weeks. The mean lymph node yield was 21.1 ± 10.4 nodes, with one patient found to have 1 lymph node involved. All resections were reported to be R0. The mean length of stay was 11.8 ± 6.2 days. At the time of analysis, one death was reported at 35 months postoperatively. Two cases of recurrence were reported at 16 months (surgical bed) and 33 months (pulmonary). All other patients remain alive and under active surveillance. The current overall survival is 26.6 ± 20.7 months and counting. Complete primary pathological response is uncommon but possible following neoadjuvant treatment in patients with PDAC. Further work to identify the common denominator within this unique cohort may lead to advances in the therapeutic approach and offer hope for patients diagnosed with borderline or locally advanced pancreatic ductal adenocarcinoma.

Variation in outcomes and practice patterns among patients with localized pancreatic cancer: the impact of the pancreatic cancer multidisciplinary clinic.

Patients with localized pancreatic adenocarcinoma (PDAC) benefit from multi-modality therapy. Whether care patterns and oncologic outcomes vary if a patient was seen through a pancreatic multi-disciplinary clinic (PMDC) versus only individual specialty clinics is unclear. Using institutional Pancreatic Cancer Registry, we identified patients with localized PDAC from 2019- 2022 who eventually underwent resection. It was our standard practice for borderline resectable (BRPC) patients to undergo ≤4 months of neoadjuvant chemotherapy, ± radiation, followed by exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation and potential exploration. Descriptive and multivariable analyses (MVA) were performed to examine the association between clinic type (PMDC vs individual specialty clinics i.e. surgical oncology, medical oncology, or radiation oncology) and study outcomes. A total of 416 patients met inclusion criteria. Of these, 267 (64.2%) had PMDC visits. PMDC group received radiation therapy more commonly (53.9% versus 27.5%, p=0.001), as compared to individual specialty clinic group. Completion of neoadjuvant treatment (NAT) was far more frequent in patients seen through PMDC compared to patients seen through individual specialty clinics (69.3% vs 48.9%). On MVA, PMDC group was significantly associated with receipt of NAT per institutional standards (adjusted OR 2.23, 95% CI 1.46-7.07, p=0.006). Moreover, the average treatment effect of PMDC on progression-free survival (PFS) was 4.45 (95CI: 0.87-8.03) months. No significant association between overall survival (OS) and clinic type was observed. Provision of care through PMDC was associated with significantly higher odds of completing NAT per institutional standards as compared to individual specialty clinics, which possibly translated into improved PFS. The development of multidisciplinary clinics for management of pancreatic cancer should be incentivized, and any barriers to such development should be addressed.

Randomized Controlled Trial of Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy Versus Long-Course Chemoradiotherapy in Locally Advanced Rectal Cancer: Comparison of Overall Response Rates.

Management of locally advanced rectal cancer (LARC) is evolving with current emphasis on the addition of chemotherapy to short course radiotherapy (SCRT). We primarily aimed to analyse the difference in overall response rates between SCRT with sequential chemotherapy and standard long-course chemoradiotherapy (LCCRT)in LARC. After randomization, patients in arm A received 45Gy in 25 fractions over 5weeks with concurrent capecitabine while patients in arm B received 25Gy in 5 fractions over 1week followed by 3 cycles of CAPOX (capecitabine and oxaliplatin) chemotherapy. Clinical and radiological response assessment was made after the completion of neoadjuvant treatment, a week prior to surgery. Adjuvant chemotherapy was added to complete 6months of peri-operative chemotherapy. Surgery was performed between 8 and 10weeks of completion of radiation treatment in both arms. Of the 33 patients recruited in this study between February 2020 to July 2021, 17 patients were randomized to arm A and 16 to arm B. The rates of complete tumour regression were 23.1% in arm A versus 35.7% in arm B (p-value = 0.683). Pathological complete response (pCR) rate was 20% arm A versus 30% in arm B (0.446). A higher number of patients in arm B experienced grade 3 diarrhoea, whereas acute skin toxicity was seen only in arm A. SCRT had fewer treatment interruptions compared to LCCRT. SCRT followed by three cycles of CAPOX chemotherapy in the neoadjuvant setting is comparable to LCCRT in terms of tumour response. This may be a better alternative regimen with fewer treatment interruptions in a resource-limited setting.

Alterations in immune cell phenotype and cytotoxic capacity in HER2+ breast cancer patients receiving HER2-targeted neo-adjuvant therapy.

The phase II neo-adjuvant clinical trial ICORG10-05 (NCT01485926) compared chemotherapy in combination with trastuzumab, lapatinib or both in patients with HER2+ breast cancer. We studied circulating immune cells looking for alterations in phenotype, genotype and cytotoxic capacity (direct and antibody-dependent cell-mediated cytotoxicity (ADCC)) in the context of treatment response. Peripheral blood mononuclear cells (PBMCs) were isolated from pre- (n = 41) and post- (n = 25) neo-adjuvant treatment blood samples. Direct/trastuzumab-ADCC cytotoxicity of patient-derived PBMCs against K562/SKBR3 cell lines was determined ex vivo. Pembrolizumab was interrogated in 21 pre-treatment PBMC ADCC assays. Thirty-nine pre-treatment and 21 post-treatment PBMC samples were immunophenotyped. Fc receptor genotype, tumour infiltrating lymphocyte (TIL) levels and oestrogen receptor (ER) status were quantified. Treatment attenuated the cytotoxicity/ADCC of PBMCs. CD3+/CD4+/CD8+ T cells increased following therapy, while CD56+ NK cells/CD14+ monocytes/CD19+ B cells decreased with significant post-treatment immune cell changes confined to patients with residual disease. Pembrolizumab-augmented ex vivo PBMC ADCC activity was associated with residual disease, but not pathological complete response. Pembrolizumab-responsive PBMCs were associated with lower baseline TIL levels and ER+ tumours. PBMCs display altered phenotype and function following completion of neo-adjuvant treatment. Anti-PD-1-responsive PBMCs in ex vivo ADCC assays may be a biomarker of treatment response.

Role of plasma circulating HER2/EFTUD2 ratio in predicting pathological complete response (pCR) after neoadjuvant dual anti-HER2 therapy in HER2-positive breast cancer (HER2+ BC).

e12592 Background: Achieving pCR following neoadjuvant chemo and anti-HER2 therapy is associated with a significantly better survival in HER2+ BC. There is currently a lack of a robust biomarker to predict pCR in HER2+ BC. Using EFTUD2 as chromosome 17 reference probe, circulating HER2/EFTUD2 plasma DNA copy number ratio (H-ratio) detected by droplet digital PCR (ddPCR) was shown to have high concordance with the tumor HER2 status. We aim to evaluate whether the change in H-ratio is associated with response to neoadjuvant dual anti-HER2 therapy. Methods: We prospectively recruited patients with HER2+ BC who received neoadjuvant taxane, trastuzumab and pertuzumab followed by radical surgery from May 2019 to April 2022. Serial plasma samples (n = 49) were collected at pre-treatment (Tpre), at 4th cycle (Tmid) and at completion of neoadjuvant treatment (Tpost). H-ratio was determined in each plasma sample using droplet ddPCR (QX200 ddPCR system, Bio-rad). H-ratio responders were defined as patients having a declining Tpost H-ratio, whereas patients having a rising or persistent Tpost H-ratio were defined as H-ratio non-responders. The relationship between pCR, H-ratio and various clinicopathological characteristics were evaluated by Spearman’s correlation, Fisher’s exact test and Wilcoxon signed-rank test. Results: Eighteen clinical stage II or III HER2+ BC patients with a median age of 56 years old (range 33 - 71) were included. The median H-ratio at Tpre, Tmid and Tpost were 1.27, 1.12 and 1.10, respectively. Higher Tpre H-ratio was significantly associated with larger tumor size (p = 0.004) and higher tumor grade (G1-2 vs G3; median H-ratio 1.15 vs 1.78; p = 0.024). Six patients (33.3%) were H-ratio responders. Ten (55.6%) of 18 patients achieved pCR after completion of neoadjuvant treatment. The pCR rate in H-ratio responders was significantly higher than the H-ratio non-responders (100% vs. 36.4%; p = 0.017). In predicting pCR, H-ratio response outperformed hormonal receptor (HR) negativity (HR- vs HR+; 72.7% vs 28.6%; p = 0.088) or high tumor grade (G1-2 vs G3; 66.7% vs 33.3%; p = 0.201). There was no association between pCR and Tpre/Tmid/Tpost H-ratio. With a median follow up of 22.8 months (range 8.2 - 41.8), there were no relapse or death. Conclusions: A high pre-treatment plasma circulating HER2/EFTUD2 ratio is associated with large tumor size and high tumor grade in HER2+ BC. The decline of HER2/EFTUD2 ratio after neoadjuvant dual anti-HER2 therapy predicts pCR, and may serve as a potential biomarker for treatment de-escalation.

Contrast-enhanced mammography in the assessment of residual disease after neoadjuvant treatment.

To investigate the utility of contrast-enhanced mammography (CEM) as an alternative to breast MRI for the evaluation of residual disease after neoadjuvant treatment (NAT). This prospective study enrolled consecutive women undergoing NAT for breast cancer from July 2017-July 2019. Breast MRI and CEM exams performed after completion of NAT were read independently by two breast radiologists. Residual disease and lesion size on MRI and CEM recombined (RI) and low-energy images (LEI) were compared. Histopathology was considered the reference standard. Statistical analysis was performed using McNemar's and Leisenring's tests. Multiple comparison adjustment was made using Bonferroni procedure. Lesion sizes were correlated using Kendall's tau coefficient. There were 110 participants with 115 breast cancers. Residual disease (invasive cancer or ductal carcinoma in situ) was detected in 83/115 (72%) lesions on pathology, 71/115 (62%) on MRI, 55/115 (48%) on CEM RI, and 75/115 (65%) on CEM LEI. When using multiple comparison adjustment, no significant differences were detected between MRI combined with CEM LEI and CEM RI combined with CEM LEI, in terms of accuracy (MRI: 77%, CEM: 72%; p ≥ 0.99), sensitivity (MRI: 88%, CEM: 81%; p ≥ 0.99), specificity (MRI: 47%, CEM: 50%; p ≥ 0.99), PPV (MRI: 81%, CEM: 81%; p ≥ 0.99), or NPV (MRI: 60%, CEM: 50%; p ≥ 0.99). Size correlation between pathology and both MRI combined with CEM LEI and CEM RI combined with CEM LEI was moderate: τ = 0. 36 vs 0.33 (p ≥ 0.99). Contrast-enhanced mammography is an acceptable alternative to breast MRI for the detection of residual disease after neoadjuvant treatment.

Clinical Implications of FDG-PET in Pancreatic Ductal Adenocarcinoma Patients Treated with Neoadjuvant Therapy

PurposeTo evaluate the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy. MethodsAmong 285 consecutive patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma between 2015 and 2021, 86 who underwent preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography after completion of neoadjuvant treatment were reviewed. Among preoperative factors, including post-treatment maximum standardized uptake value, predictors of early recurrence and poor prognosis were identified using multivariate analysis for decision making in surgery. ResultsNineteen (22%) patients with pancreatic ductal adenocarcinoma demonstrated high maximum standardized uptake (≥ 4.5). High post-treatment maximum standardized uptake (≥ 4.5) predicted early recurrence within 6 months after surgery and correlated with shorter recurrence-free survival. Elevated post-treatment CA19-9 level (> 37 U/ml) and maximum standardized uptake ≥ 4.5 were independent prognostic factors. Post-treatment, a high maximum standardized uptake value indicated a poorer prognosis than a low maximum standardized uptake value in both patients with elevated CA19-9 and normal CA19-9 levels. The median overall survival in patients with elevated post-treatment CA19-9 and high maximum standardized uptake was only 17 months; 67% experienced early recurrence. Dynamic changes in maximum standardized uptake during neoadjuvant therapy were correlated with pathological response to neoadjuvant therapy, but not with radiological response or change in CA19-9 level. ConclusionsPost-treatment assessment using maximum standardized uptake value is useful for stratifying patients with pancreatic ductal adenocarcinoma who will benefit from surgery. Instead of subsequent curative resection, additional neoadjuvant therapy should be considered in patients with a persistently high maximum standardized uptake value.

Comprehensive 18F-FDG PET-based radiomics in elevating the pathological response to neoadjuvant immunochemotherapy for resectable stage III non-small-cell lung cancer: A pilot study.

To develop a comprehensive PET radiomics model to predict the pathological response after neoadjuvant toripalimab with chemotherapy in resectable stage III non-small-cell lung cancer (NSCLC) patients. Stage III NSCLC patients who received three cycles of neoadjuvant toripalimab with chemotherapy and underwent 18F-FDG PET/CT were enrolled. Baseline 18F-FDG PET/CT was performed before treatment, and preoperative 18F-FDG PET/CT was performed three weeks after the completion of neoadjuvant treatment. Surgical resection was performed 4-5 weeks after the completion of neoadjuvant treatment. Standardized uptake value (SUV) statistics features and radiomics features were derived from baseline and preoperative PET images. Delta features were derived. The radiologic response and metabolic response were assessed by iRECIST and iPERCIST, respectively. The correlations between PD-L1 expression, driver-gene status, peripheral blood biomarkers, and the pathological responses (complete pathological response [CPR]; major pathological response [MPR]) were assessed. Associations between PET features and pathological responses were evaluated by logistic regression. Thirty patients underwent surgery and 29 of them performed preoperative PET/CT. Twenty patients achieved MPR and 16 of them achieved CPR. In univariate analysis, five SUV statistics features and two radiomics features were significantly associated with pathological responses. In multi-variate analysis, SUVmax, SUVpeak, SULpeak, and End-PET-GLDM-LargeDependenceHighGrayLevelEmphasis (End-GLDM-LDHGLE) were independently associated with CPR. SUVpeak and SULpeak performed better than SUVmax and SULmax for MPR prediction. No significant correlation, neither between the radiologic response and the pathological response, nor among PD-L1, driver gene status, and baseline PET features was found. Inflammatory response biomarkers by peripheral blood showed no difference in different treatment responses. The logistic regression model using comprehensive PET features contributed to predicting the pathological response after neoadjuvant toripalimab with chemotherapy in resectable stage III NSCLC patients.

Abstract OT1-12-06: Neoadjuvant pyrotinib versus pertuzumab in combination with trastuzumab and nab-Paclitaxel for patients with HER2-positive early or locally advanced breast cancer (Pyramid): A randomized, multicenter, open-label, phase 2 trial

Abstract Background: Pyrotinib is an irreversible pan-ErbB receptor tyrosine kinase inhibitor targeting human epidermal growth factor receptor 1 (HER1), HER2, and HER4. Exploratory studies of neoadjuvant pyrotinib combined with trastuzumab-based standard chemotherapy for HER2-positive (HER2+) early or locally advanced breast cancer (BC) showed promising pathological complete response (pCR) rates of 51.6%-71%, with a manageable toxicity profile. We are to further investigate this combination strategy versus standard therapy in a randomized trial. Trial design: Pyramid is a randomized, multicenter, open-label, two-stage adaptive enrichment phase 2 trial to evaluate the efficacy and safety of pyrotinib plus trastuzumab and nab-Paclitaxel versus pertuzumab plus trastuzumab and nab-Paclitaxel as neoadjuvant treatment in patients with HER2+ early or locally advanced BC (NCT04900311). Eligible patients will be randomized 1:1 to receive four 21-day cycles of pyrotinib (400 mg, po, qd) or pertuzumab (840 mg loading dose, 420 mg maintenance doses, i.v., day 1) with trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance doses, i.v., day 1) and nab-Paclitaxel (260 mg/m2, day 1 or 125 mg/m2, i.v., day 1/8/15). After completion of neoadjuvant treatment, patients will undergo surgery, followed by standard EC regime for 4 cycles. Subsequent adjuvant therapy will be decided by investigators. Randomization was stratified by hormone receptor (HR) status (ER and/or PR positive vs. negative) and primary tumor size (2<T≤5 cm vs. T>5 cm). There will be two stage of this trial, and population may be enriched to HR-positive based on the results of interim analysis at Stage I. Eligibility criteria: Key inclusion criteria include female, treatment-naïve, histologically confirmed HER2+ invasive BC (cT2-4/cN0-3/cM0), the diameter of primary tumor > 2 cm, known HR status (ER and PR). Specific aims: Primary endpoint is total pathologic complete response (tpCR) rate per central review assessment. Secondary endpoints include invasive disease-free survival, event-free survival, objective response rate, breast-conserving surgery rate, safety. Exploratory endpoint is to investigate the possible predictive biomarkers of efficacy. Statistical methods: A sample size of 220 patients per arm is calculated to provide a power of 80% with a significance level of 0.1 (one-sided) to detect an estimated increase in the tpCR rate from 39% in the pertuzumab group to 49% in the pyrotinib group. Considering a dropout rate of 10%, 490 patients (245 per arm) will be required to be enrolled. A two-stage adaptive enrichment design will be used. The trial will enroll 186 patients at Stage I and an interim analysis will be conducted by an independent data monitoring committee (IDMC) when the pathologic response has been evaluated in at least 132 patients (including at least 66 HR-positive patients) at Stage I. Then, one of five options might be adapted at Stage II depending on the results, including: i. Continue study as planned in whole population; ii. Re-estimate sample size in whole population; iii. Enrich to HR-positive population with pre-defined sample size; iv. Enrich to HR-positive population and re-estimate sample size; v. Early termination. The Clopper-Pearson method will be used to calculate a 95% confidence interval (CI) for the tpCR rate. The CMH chi-square test will be used to compare the tpCR rate between groups and 95% CIs for the difference will be estimated using the Miettinen-Nurminen method. Present accrual and target accrual: Target enrollment will be 490 patients at approximately 20 sites in China. As of June 24, 2021, 4 patients have been enrolled. Contact information: Jin Zhang, MD, Email: zhangjin@tjmuch.com. Citation Format: Jin Zhang, Qiang Liu, Hongchuan Jiang, Jianguo Zhang, Jianghua Ou, Dedian Chen, Fuguo Tian, Yongqing Li, Xiaoming Cheng, Zhong Ouyang. Neoadjuvant pyrotinib versus pertuzumab in combination with trastuzumab and nab-Paclitaxel for patients with HER2-positive early or locally advanced breast cancer (Pyramid): A randomized, multicenter, open-label, phase 2 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-12-06.

The efficacy and safety of neoadjuvant camrelizumab and chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma.

278 Background: To explore the efficacy and safety of neoadjuvant camrelizumab and chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma (ESCC) by an open label, single-arm, phase 2 clinical trial (ClinicalTrials.gov, Identifier number: NCT04506138). Methods: The eligible patients were arranged to receive 2 cycles of camrelizumab (200mg, day 1) combined with carboplatin (AUC = 5, day 1) and albumin paclitaxel (100 mg/m2, day 1, 8). All treatments were given intravenously in 3-week cycle. Patients underwent surgery within 4-6 weeks after the completion of neoadjuvant treatment. The primary endpoint was pathologic complete response (pCR), and secondary endpoints were major pathological response (MPR), safety and feasibility. The quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) scale and EQ-5D-3L scale. Results: A total of 46 patients were recruited, among whom the clinical stage II, III, and IVa at baseline were 11 (23.9%), 33 (71.7%), and 2 (4.3%), respectively. Forty-five patients completed 2 cycles of neoadjuvant treatment. One patient received 1 cycle of neoadjuvant treatment and then lost to be followed up. Eight patients did not receive surgery. Except 1 patient accept exploratory surgery, 37 patients (37/46, 80.4%) achieved R0 resection. Eight patients (8/37, 21.6%) had pCR in both primary tumors and lymph nodes. MPR of primary tumors and lymph nodes was observed in 18 patients (18/37, 48.6%). During neoadjuvant treatment period, all 46 patients presented with treatment-related AEs (TRAEs) of any grade. Seven patients (7/46,15.2%) experienced grade ≥ 3 TRAEs. One patient suffered grade 5 immune-associated pneumonia. The most common TRAEs were anemia (32/46, 70.0%), followed by thrombocytopenia (15, 32.6%), leukopenia (14, 30.4%), neutropenia (13, 28.3%), rash (12, 26.1%), reactive cutaneous capillary endothelial proliferation (RCCEP) (7, 15.2%). The median interval between the first cycle of neoadjuvant treatment and surgery was 64 days (range, 56-77 days). Symptom scores in FACT-E scale were improved by neoadjuvant treatment (t = -2.60, P = 0.01). PD-L1 CPS (< 10 vs ≥ 10), PD-L1 TPS (< 1% vs ≥ 1%) and TMB (split according to top 20% of TMB value) had no effect on the pCR rate and MPR rate. Conclusions: Neoadjuvant camrelizumab combined with chemotherapy achieved a promising pathologic response, which was effective and safe. Meanwhile, neoadjuvant treatment improved QoL of patients. Some larger multi-center trials are undergoing for further confirmation of efficacy and safety. Clinical trial information: NCT04506138.

Role of Nutritional Status in the Treatment Outcome for Esophageal Squamous Cell Carcinoma.

Undernourishment is reported to impair treatment response, further leading to poor prognosis for cancer patients. We aimed to investigate the role of nutritional status on the prognosis of squamous cell carcinoma (SCC) of the esophagus, and its correlation with anticancer immune responsiveness. We retrospectively reviewed 340 esophageal-SCC patients who completed curative treatment and received a nutrition evaluation by the Patient-Generated Subjective Global Assessment (PGSGA) score at the beginning and completion of neoadjuvant treatment at our hospital. The correlation between the nutritional status and various clinicopathological parameters and prognosis were examined. In addition, the role of nutritional status in the regulation of the anticancer immune response was also assessed in cancer patients and in a 4-nitroquinoline 1-oxide (4NQO)-induced esophageal tumor model. Our data revealed that malnutrition (patients with a high PGSGA score) was associated with advanced stage and reduced survival rate. Patients in the group with a high PGSGA score were correlated with the higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived-suppressor cells (MDSC) and increased IL-6 level. Furthermore, surgical resection brought the survival benefit to patients in the low PGSGA group, but not for the malnourished patients after neoadjuvant treatment. Using a 4NQO-induced tumor model, we found that nutrition supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. In conclusion, malnutrition was associated with poor prognosis in esophageal-SCC patients. Nutritional status evaluated by PGSGA may be useful to guide treatment decisions in clinical practice. Nutritional supplementation is suggested to improve prognosis, and it might be related to augmented anticancer immune response.

Surgery for periampullary pancreatic cancer

Periampulläre Neoplasien sind eine heterogene Gruppe verschiedener Tumorentitäten der periampullären Region, von denen das Pankreasadenokarzinom mit 60–70 % am häufigsten ist. Wie typisch für Pankreaskarzinome zeichnen sich periampulläre Pankreaskarzinome durch ein aggressives Wachstum und eine frühe systemische Progression aus. Aufgrund ihrer besonderen Lage in unmittelbarer Nähe zur Papilla Vateri treten Symptome in eher früherem Tumorstadium auf, sodass die Therapiemöglichkeiten und Prognose insgesamt günstiger sind als bei Pankreaskarzinomen anderer Lokalisation. Trotzdem unterscheiden sich die Therapieprinzipien bei periampullären Pankreaskarzinomen nicht wesentlich von den Standards bei Pankreaskarzinomen anderer Lokalisation. Ein potenziell kurativer Therapieansatz beim nichtmetastasierten periampullären Pankreaskarzinom ist multimodal und besteht aus der Durchführung einer partiellen Duodenopankreatektomie als radikale onkologische Resektion in Kombination mit einer systemischen, meist adjuvant verabreichten Chemotherapie. Bei Patienten mit günstigen prognostischen Faktoren kann hierdurch ein Langzeitüberleben erzielt werden. Zudem wurden mit der Weiterentwicklung der Chirurgie und Systemtherapie auch potenziell kurative Therapiekonzepte für fortgeschrittene, früher irresektable Tumoren etabliert, welche nun nach Durchführung einer neoadjuvanten Therapie oft einer Resektion zugeführt werden können. In diesem Beitrag werden die aktuellen chirurgischen Prinzipien der radikalen onkologischen Resektion periampullärer Pankreaskarzinome im Kontext der multimodalen Therapie dargestellt und ein Ausblick auf mögliche künftige Entwicklungen der Therapie gegeben.

Short-course radiotherapy with consolidation chemotherapy versus conventionally fractionated long-course chemoradiotherapy for locally advanced rectal cancer: randomized clinical trial.

The trial hypothesis was that, in a resource-constrained situation, short-course radiotherapy would improve treatment compliance compared with conventional chemoradiotherapy for locally advanced rectal cancer, without compromising oncological outcomes. In this open-label RCT, patients with cT3, cT4 or node-positive non-metastatic rectal cancer were allocated randomly to 5 × 5 Gy radiotherapy and two cycles of XELOX (arm A) or chemoradiotherapy with concurrent capecitabine (arm B), followed by total mesorectal excision in both arms. All patients received a further six cycles of adjuvant chemotherapy with the XELOX regimen. The primary endpoint was treatment compliance, defined as the ability to complete planned treatment, including neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy to a dose of six cycles. Of 162 allocated patients, 140 were eligible for analysis: 69 in arm A and 71 in arm B. Compliance with planned treatment (primary endpoint) was greater in arm A (63 versus 41 per cent; P = 0.005). The incidence of acute toxicities of neoadjuvant therapy was similar (haematological: 28 versus 32 per cent, P = 0.533; gastrointestinal: 14 versus 21 per cent, P = 0.305; grade III-IV: 2 versus 4 per cent, P = 1.000). Delays in radiotherapy were less common in arm A (9 versus 45 per cent; P < 0.001), and overall times for completion of neoadjuvant treatment were shorter (P < 0.001). The rates of R0 resection (87 versus 90 per cent; P = 0.554), sphincter preservation (32 versus 35 per cent; P = 0.708), pathological complete response (12 versus 10 per cent; P = 0.740), and overall tumour downstaging (75 versus 75 per cent; P = 0.920) were similar. Downstaging of the primary tumour (ypT) was more common in arm A (P = 0.044). There was no difference in postoperative complications between trial arms (P = 0.838). Reduced treatment delays and a higher rate of compliance were observed with treatment for short-course radiotherapy with consolidation chemotherapy, with no difference in early oncological surgical outcomes. In time- and resource-constrained rectal cancer units in developing countries, short-course radiotherapy should be the standard of care.