Clinical Downstaging Research Articles

Preliminary analysis of PD-1 inhibitors combined with chemotherapy as neoadjuvant therapy for local advanced non-small cell lung cancer (NSCLC).

200 Background: The benefits of neoadjuvant immunotherapy and chemotherapy for resectable NSCLC suggest that this combined treatment may provide more surgical opportunities and survival benefits for potentially resectable locally advanced NSCLC. Methods: We retrospectively collected data from 28 patients with stage III EGFR/ALK/ROS wild-type NSCLC. Eligible patients received 2-8 cycles of neoadjuvant chemoimmunotherapy (squamous carcinoma: PD-1 inhibitor combined with albumin-bound paclitaxel and cisplatin/carboplatin; adenocarcinoma: PD-1 inhibitor combined with pemetrexed and carboplatin), followed by re-evaluation for surgery. Afterwards, patients underwent surgery after downstaging, with some receiving adjuvant immunotherapy maintenance for one year. Primary endpoints included major pathological response (MPR), pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: All 28 patients were male, with 7 (25%) in stage IIIA, 10 (35.7%) in IIIB, 4 (14.3%) in IIIC, 2 (7.14%) in IVA, and 2 (7.14%) in IVB. There were 22 cases of squamous cell carcinoma, 4 of adenocarcinoma, 1 of large cell lung cancer, and 1 of lymphoepithelioma-like carcinoma. 23 patients (82.1%) completed neoadjuvant treatment and underwent resection, achieving 100% R0 resection rate (23/23); 5 patients did not undergo surgery, 3 of whom received combined radiochemotherapy due to disease progression, 1 delayed surgery due to immunotherapy associated myocardial damage, and 1 died from massive hemoptysis and hemorrhagic shock. The objective response rate (ORR) was 60.7%, 95%CI [40.6-78.5%] and the disease control rate (DCR) was 85.7%, 95%CI [67.3-96.0%]. Among the 23 patients who underwent surgery, the pCR was 60.9%, 95%CI [38.5-80.3%], MPR was 4.3%, 95%CI [0.1-21.9%], clinical downstaging rate was 50%, 95%CI [30.6-69.4%] and pathological downstaging rate was 86.9%, 95%CI [66.4-97.2%]. 17 patients (77.3%) underwent lobectomy, and 5 (22.7%) underwent bilobectomy with a median blood loss of 100 ml, IQR [55.0-100]. There were no surgery-related deaths. Postoperatively, one patient developed chylothorax, one had a lung infection, and the two improved after conservative treatment. 11 patients (47.8%) received post-surgery immunotherapy maintenance, and 2 of them (8.7%) developed immune-related pneumonia. As of April 7, 2024, the median follow-up time was 21.5 months (95%CI: 17-34 Mo), At 12 months。 PFS rate was 82.1% (95%CI: 69.1-97.6%); OS rate was 96.3% (95%CI: 89.4-100%). Conclusions: Neoadjuvant immunotherapy combined with surgery for unresectable locally advanced NSCLC may benefit patients and significantly extend survival.

Pancreatic Cancer with Vascular Involvement: Adherence to Current Standard-of-Care Associated with Improved Survival.

This study is a retrospective cohort study of National Cancer Data Base (NCDB) data for pancreatic cancer with vascular involvement. A total of 23903 patients with vascular involvement were included and divided into 3 groups; no treatment (40.6%), medical treatment (36.6%), and resection (22.8%). Of the patients undergoing resection, 31.3% received neoadjuvant multiagent chemotherapy (N-MAC). The remainder were treated with postoperative adjuvant treatment (33.8%), surgery alone (24.9%), preoperative radiotherapy (8.3%), or single-agent preoperative chemotherapy (1.7%). Median survival for N-MAC was superior (28.42 months) when compared to neoadjuvant radiotherapy (20.73 months), neoadjuvant single-agent chemotherapy (20.8 months), postoperative adjuvant therapy (17.87 months), and surgery alone (10.12 months). N-MAC was associated with improved survival compared to postoperative multiagent chemotherapy (P-MAC) (28.4 vs 16.95, HR 1.82; CI 1.64-2.02, P < .0010) (Figure 1). The addition of radiation therapy to N-MAC did not improve survival (27.4 vs 29.8, HR .93; CI .83-1.05, P = .3). Clinical downstaging occurred in 40% of patients treated with N-MAC, and downstaging was associated with improved survival (HR .74; CI .64-.85, P < .001). N-MAC patients were more likely to undergo an R0 resection than P-MAC (74% v. 48, P < .001). Most resected pancreatic cancer patients in this study with vascular involvement receive either postoperative or no adjuvant therapy. N-MAC increases downstaging, R0 resection rates, and survival.

520. EFFICACY AND SAFETY OF NEOADJUVANT CHEMOTHERAPY AND IMMUNOTHERAPY IN LOCALLY RESECTABLE ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Compared with neoadjuvant chemotherapy, concurrent chemoradiotherapy can significantly increase pCR rate and improve overall survival of Locally Advanced ESCC. However, the major pattern of failure is distant metastasis, and the increased risk of adverse events and surgery. Adding PD-1 inhibitor to the chemotherapy have shown significant clinical benefits and become the standard of care for first-line treatment of ESCC. We investigate the efficacy and safety of neoadjuvant PD-1 blockade combined with chemotherapy in real world. We performed a retrospective, single institution review of all resectable locally advanced ESCC patients who received neoadjuvant sintilimab combined with chemotherapy and completed surgery in the sixth medical center of PLA general hospital from December 2019 to February 2022. The primary outcome was pCR rate in both the primary tumor and lymph nodes. Secondary outcomes were R0 resection rate, MPR rate, tumor downstaging rate, surgical complications, and treatment-related adverse events (TRAEs). 37 Patients aged between 47 to 76 years old (median age, 62) were collected. 3(8.1%) were diagnosed with stage II ESCC, 30(81.1%) with stage III, and 7(18.9%) with stage IVA (AJCC 8th). 30(81.1%) were male. 31 patients received 2 cycles and 6 patients received 3 cycles. 5(13.5%) patients obtained pCR. 7(18.9%) patients obtained pCR in primary tumor. 36(97.3%) patients obtained R0 resection. MPR (PCR included) was achieved in 18 (48.6%) patients. 28(75.7%) patients achieved clinical downstaging, and 64.9 (%) achieved pathological downstaging. Grade 3-4 TRAEs occurred in 7(18.9%) patients, and grade 3-4 surgical complications occurred in 1(2.7%) patient. These real-world data revealed that neoadjuvant sintilimab plus chemotherapy could provide benefits with good tolerability for resectable locally advanced ESCC, and warrants further exploration in prospective clinical studies.

Rescue Surgery after Immunotherapy/Tyrosine Kinase Inhibitors for Initially Unresectable Lung Cancer

Simple SummaryLocally advanced or metastatic non-small cell lung cancer (NSCLC) has been considered for a long time as an unresectable disease. Chemotherapy was considered the only therapeutic option for these conditions and the results were unsatisfactory. Recent advances in biology and immunology have led to the use of personalized treatments by using tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), which produce significant and durable treatment responses. Large trials explored the utility of TKIs and ICIs in neoadjuvant or adjuvant settings, showing good results in terms of radiological response and long-term outcomes. Retrospective case series in patients with the previously unresectable disease who received treatment with TKIs, or ICIs showed important clinical changes that consider the possibility of pulmonary resection of the residual disease. They showed an overall feasibility for pulmonary resection but also raised concerns about the technical challenges. In the present study, we analyzed and reported the surgical and long-term outcomes of patients with initial unresectable, locally advanced, or oligometastatic NSCLC who were treated with TKIs or ICIs achieving a clinical downstaging so as to re-enter resectability.Background: We report the outcomes for unresectable patients with locally advanced or oligometastatic non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitor (TKI) or immunotherapy who achieved a clinical downstaging so as to re-enter resectability. Methods: We retrospectively reviewed the clinical, surgical, and pathological data of 42 patients with histologically proven, inoperable NSCLC who received rescue surgery after a good response to TKI or immunotherapy between March 2014 and December 2021. Results: Of 42 patients, 39 underwent pulmonary resection with therapeutic intent (three explorative thoracotomies). There were 26 males, with a median age of 64 years (range, 41–78 years). Twenty-three patients received TKIs and 19 immunotherapies. Anatomic resection was performed in 97.4% of resected patients (38/39) including 30 lobectomies, one right upper sleeve lobectomy, five pneumonectomies, one tracheal sleeve pneumonectomy, and one bilobectomy; a patient underwent wedge resection. Of 10 procedures attempted via a robotic approach, two required conversion to thoracotomy. No intraoperative morbidity/mortality occurred. The median operative time was 190 (range, 80–426) minutes; estimated blood loss was 200 mL (range, 35–780 mL). Morbidity occurred in 13/39 (33.3%). The median length of hospital stay was 6.5 days (range, 4–23 days). Pathologic downstaging was 74.4% (29/39). With a median follow-up of 28.7 months, the 5-year disease-free interval was 46.5%, and the 5-year overall survival was 66.0%; 32/39 patients (82.1%) are alive, 10 with the disease. Conclusions: Lung resection for suspected residual disease after immunotherapy or TKIs is feasible, with encouraging pathological downstaging. Surgical operation may be technically challenging due to the presence of fibrosis, but significant morbidity appears to be rare. Outcomes are encouraging, with reasonable survival during the short-interval follow-up.

Quality of life in a randomized trial comparing two neoadjuvant regimens for locally advanced rectal cancer-INCAGI004.

Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC), but the emergence of different drug regimens may result in different response rates. Good clinical response translates into greater sphincter preservation, but quality of life (QOL) may be impaired after treatment due to chemoradiotherapy and surgical side effects. To prospectively evaluate the impact of clinical response and surgical resection on QOL in a randomized trial comparing two different neoCRT regimens. Stage II and III rectal cancer patients were randomized to receive neoCRT with either capecitabine (group 1) or 5-Fu and leucovorin (group 2) concomitant to long-course radiotherapy. Clinical downstaging was accessed using MRI 6-8weeks after treatment. EORTCs QLQ-C30 and CR38 were applied before treatment (T0), after neoCRT (T1), after rectal resection (T2), early after adjuvant chemotherapy (T3), and 1year after the end of treatment or stoma closure (T4). The Wexner scale was used for fecal incontinence evaluation at T4. A C30SummaryScore (Geisinger and cols.) was calculated to compare QOL results. Thirty-two patients were assigned to group 1 and 31 to group 2. Clinical downstaging occurred in 70.0% of group 1 and 53.3% of group 2 (p = 0.288), and sphincter preservation was 83.3% in group 1 and 80.0% in group 2 (p = 0.111). No significant difference in QOL was detected when comparing the two treatment groups after neoCRT using QLQ-C30. However, the CR38 module detected differences in micturition problems (15.3 points), gastrointestinal problems (15.3 points), defecation problems (11.8 points), and sexual satisfaction (13.3 points) favoring the capecitabine group. C30SummaryScore detected significant improvement comparing T0 to T1 and deterioration comparing T1 to T2 (p = 0.025). The mean Wexner scale score was 9.2, and a high score correlated with symptoms of diarrhea and defecation problems at T4. QOL was equivalent between groups after neoCRT except for micturition problems, gastrointestinal problems, defecation problems, and sexual satisfaction favoring the capecitabine arm after. The overall QOL using the C30SummaryScore was improved after neoCRT, but decreased following rectal resection, returning to basal levels at late evaluation. Fecal incontinence was high after sphincter preservation. ClinicalTrials.gov Identifier: NCT03428529.

Neoadjuvant Sintilimab Plus Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

BackgroundNeoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT) are the standard treatments in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Adding PD-1 inhibitor to the chemotherapy has shown significant clinical benefits in first-line treatment of advanced ESCC. This study evaluated the efficacy and safety of neoadjuvant sintilimab plus chemotherapy in patients with resectable locally advanced ESCC.MethodsThe clinical data of 96 patients with resectable locally advanced ESCC, treated with sintilimab plus chemotherapy followed by esophagectomy, were reviewed. The pathologic complete response (pCR) rate, major pathological response (MPR) rate, R0 resection rate, tumor downstaging, survival, and safety were retrospectively analyzed.ResultsPatients were between the ages of 43 and 78 years (interquartile range [IQR], 60–69 years). Forty (41.7%) were diagnosed with stage II ESCC, 52 (54.2%) with stage III, and 4 (4.2%) with stage IVA. Sixty-seven (69.8%) were male, and 84 (87.5%) patients had an ECOG PS of ≤1. Forty-eight (50.0%) patients received 3–4 cycles of the neoadjuvant treatment. Twenty-nine (30.2%) patients obtained pCR, and MPR was achieved in 60 (62.5%) patients. The R0 resection rate was 99%. Eighty (83.3%) patients achieved clinical downstaging, and 71 (74.0%) achieved pathological downstaging. The median follow-up was 8.9 months, and 1-year DFS rate was 95.2% (95% CI, 88.8%–100%). Grade 3–4 TRAEs occurred in 12 (12.5%) patients, and the incidence of grade 3–4 surgical complications was 2.1%. No deaths were reported.ConclusionThese real-world data revealed that neoadjuvant sintilimab plus chemotherapy could provide encouraging pCR with good tolerability for resectable locally advanced ESCC, and this regimen warrants further exploration in prospective clinical studies.

APPLICATION OF TEXTURAL RADIOMICS AND KINETIC PARAMETERS TO QUANTIFY EARLY PHASE NEOADJUVANT CHEMOTHERAPY TREATMENT RESPONSE ON BREAST DYNAMIC CONTRAST ENHANCED MAGNETIC RESONANCE IMAGES

Breast cancer is the most commonly diagnosed disease in women as well as the leading cause of cancer death. Neoadjuvant chemotherapy (NAC) is a standard treatment technique for locally advanced breast tumors, with the goal of clinical downstaging. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is used to diagnose breast cancer and could be used to access the NAC treatment response. However, the assessment of treatment response at the early phase is crucial and challenging. Previous studies show that radiomic features have the potential in quantifying the pathological changes due to NAC. In this work, an attempt has been made to objectively quantify the early phase changes observed on the DCE-MRI due to NAC using radiomic features. Different radiomic features are extracted from DCE-MR images of Visit 1 (pre-treatment) &amp; 2 (post-treatment) to quantify the treatment response and are statistically analyzed. Further, kinetic features from the images are also extracted and associated with the radiomic features and are tested using Spearman’s correlation test. Results demonstrate that radiomic features such as energy, homogeneity, entropy, kurtosis have shown a highly significant difference between the two visits (p ≤ 0.05). Similarly, the association between significant radiomic features and kinetic parameters shown a positive correlation with r = (0.48 - 0.66), p = (0.00029 - 0.016) respectively. Hence it appears that the association of radiomic and kinetic parameters would be used as an adjunct measure in differentiating the NAC treatment visits at early stages.

A longitudinal study evaluating interim assessment of neoadjuvant chemotherapy for bladder cancer.

To evaluate the usefulness of radiological re-staging after two and four cycles of neoadjuvant chemotherapy (NAC), the impact of re-staging on further patient management, and the correlation between clinical and final pathological tumour stage at radical cystectomy (RC). We conducted a longitudinal, single-centre, cohort study of prospectively collected consecutive patients who underwent NAC and RC for urothelial muscle-invasive bladder cancer between July 2001 and December 2017. Patients underwent repeated computed tomography scans for re-staging after two cycles of NAC and after completion of NAC before RC. Of 180 patients, 110 had ≥four cycles of NAC and had complete imaging available. In the entire cohort, further patient management was only changed in 2/180 patients (1.1%) after two cycles of NAC based on radiological findings. Patients who were stable after two cycles but then downstaged after at least four cycles of NAC had a similarly lowered risk of death (hazard ratio [HR] 0.53). Only one patient downstaged after two cycles was subsequently upstaged after four cycles. Clinical downstaging was observed in 51 patients (46%), 55 patients (50%) had no change in clinical stage and four patients (3.6%) were clinically upstaged. Patients clinically downstaged after four cycles of NAC had a lower risk of death (HR 0.49, 95% confidence interval 0.25-0.94; P = 0.033) compared to those with no change or upstaged after completion of NAC. Re-staging of muscle-invasive bladder cancer after two cycles of NAC offers little additional information, rarely changes patient management, and may therefore be omitted, whereas re-staging after completion of NAC by CT is a strong predictor of overall survival.

Downstaging of cervical cancer in Tanzania over a 16-year period.

Globally, the highest cervical cancer mortality rates are found in East Africa. Visual inspection with acetic acid (VIA)-based screening in resource-poor settings has been shown to decrease the proportion of women presenting with late-stage cervical cancer, a process known as clinical downstaging. The only cancer treatment center in Tanzania, Ocean Road Cancer Institute (ORCI) in Dar es Salaam, opened a VIA-based cervical cancer screening program in 2002. We reviewed 6,676 medical records of cervical cancer patients at the ORCI from 2002-2011 to 2014-2018 for stage at diagnosis and screening status, among other variables. We investigated whether clinical downstaging occurred in this period among women screened at the ORCI, when compared to unscreened women. Our results indicated that the proportion of women presenting with late-stage cervical cancer among women screened at the ORCI decreased by 27.7% over the 16-year period (χ2 = 16.99; p = 0.0002). Among unscreened women, a non-significant 13.2% decrease in late-stage disease was observed (χ2 = 1.74; p = 0.4179). Our results suggest clinical downstaging occurred among women screened at the ORCI over the 16-year period, and this difference may be attributed to the screening program as the same decrease in stage was not observed among unscreened women during the same time period. At present, less than one percent of Tanzanian women receive yearly cervical cancer screenings. Access to screening through expansion of the ORCI screening clinic and the creation of more clinics should be prioritized.

Neoadjuvant Four-Drug Combination Therapy for NSCLC With EGFR Mutation Avoiding Total Pneumonectomy

We report a case of successful neoadjuvant four-drug combination therapy to avoid total pneumonectomy. A 33-year-old male patient was diagnosed with locally advanced non-squamous NSCLC harboring EGFR mutation in the left lower lobe. The patient experienced significant clinical downstaging after two cycles of neoadjuvant therapy, including icotinib, carboplatin, pemetrexed, and bevacizumab. He underwent a successful lobectomy avoiding pneumonectomy. The patient showed no recurrence in the follow-up of a chest computed tomographic scan, which is 17 months after surgery. The promising results of this neoadjuvant combination therapy provided a novel therapeutic option for patients with locally advanced EGFR-mutated NSCLC facing total pneumonectomy.

Abstract OT3-01-01: Feasibility of carbon tattooing for targeted lymph node biopsy in breast cancer patients treated by primary systemic therapy (TATTOO trial)

Abstract Background: Selective removal of initially suspicious axillary lymph nodes in breast cancer patients downstaged by primary systemic therapy (PST) improves the accuracy of surgical staging and provides the opportunity for less extensive axillary surgery. Different techniques for this targeted lymph node biopsy (TLNB) have been evaluated. These are either prohibited for radiation safety reasons (radioactive seeds) in some countries, or revealed low identification rates for the target lymph node (TLN) in prospective feasibility trials (wire localization of clip-marked TLN). Therefore, an alternative TLN marking procedure avoiding radiation exposure, specialized intraoperative equipment, high costs and preoperative localization procedures is urgently needed. Tattooing TLNs with highly purified carbon suspension prior to PST and identifying the TLN intraoperatively by visual examination, is a method combining low costs with high patient comfort. Because of the data scarcity on the feasibility of TLNB by carbon tattooing, the TATTOO trial was initiated. Trial design: The Tattoo trial is a single-arm, multicentric, prospective feasibility trial. Before initiation of PST, ultrasound-guided fine needle aspiration or core needle biopsy of the most suspicious ipsilateral axillary lymph node (TLN) is performed and a highly purified carbon suspension then injected into the cortex of the sampled lymph node and the adjacent soft tissue. After completion of PST, TLNB and axillary lymph node dissection Level I/II is performed in all patients. In those with clinical and sonographical axillary down-staging, sentinel lymph node (SLN) biopsy is additionally performed. Eligibility criteria: Prior to tattooing, written informed consent is obtained. Female patients aged at least 18 years, with histologically confirmed invasive uni- or bilateral breast cancer with clinically or sonographically suspicious axillary lymph nodes and planned PST without signs of distant metastases are eligible. Specific aims: The primary outcome of the trial is the intraoperative identification rate (IR) of the carbon-labeled TLN after PST. Secondary outcomes are the concordance rate (CR) of sentinel lymph nodes (SLN) and TLN, the false negative rate (FNR) of targeted axillary dissection (TAD, i.e. SLNB biopsy + TLNB) and complications associated with the procedure. Statistical methods: IR is defined as the proportion of patients with intraoperatively visually detectable TLNs of all patients. CR is expressed as the proportion of patients in whom TLNB and SLN biopsy reveal the same lymph nodes. The proportion of patients with negative TLN and/or SLN but with metastatic axillary lymph nodes on ALND out of all patients with positive lymph nodes will be reported as FNR. Complications associated with tattooing (i.e. bleeding, pain, adverse tattoo effects) are reported. Statistical analyses will be carried out using IBM SPSS statistics version 25. Present and target accrual: Patient accrual was initiated in November 2017. Until now, 84 patients have been included by three sites in Germany and Sweden. The target enrollment of 100 patients is estimated to be reached by August 2019 and the final trial report is planned for 2020. Contact information Steffi Hartmann, MD (steffi.hartmann@kliniksued-rostock.de) Citation Format: Steffi Hartmann, Angrit Stachs, Thorsten Kühn, Antje Winckelmann, Jana de Boniface, Bernd Gerber, Toralf Reimer. Feasibility of carbon tattooing for targeted lymph node biopsy in breast cancer patients treated by primary systemic therapy (TATTOO trial) [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 OT3-01-01.

Time for a shift in molecular down staging in luminal breast cancer.

The management of locally advanced breast cancer and, in some cases, operable node-positive disease, includes neoadjuvant chemotherapy (with or without HER2-targeted therapies), surgery, and locoregional radiotherapy. Pathological complete response to neoadjuvant therapy is considered an important prognostic factor in locally advanced breast cancer, but such prognostic information is primarily relevant in triple-negative breast cancer and HER2-positive subtypes.1,2 In luminal breast cancer, systemic chemotherapy can result in clinical downstaging or clinical response, but pathological complete response is not reached in most cases making the use of this endpoint of questionable value in this subtype.

Bio-physic constraint model using spatial registration of delta 18F-fluorodeoxyglucose positron emission tomography/computed tomography images for predicting radiation pneumonitis in esophageal squamous cell carcinoma patients receiving neoadjuvant chemoradiation.

PurposeThis study integrated clinical outcomes and radiomics of advanced thoracic esophageal squamous cell carcinoma patients receiving neoadjuvant concurrent chemoradiotherapy (NACCRT) to establish a novel constraint model for predicting radiation pneumonitis (RP).Patients and methodsWe conducted a retrospective review for thoracic advanced esophageal cancer patients who received NACCRT. From 2013 to 2018, 89 patients were eligible for review. Staging workup and response evaluation included positron emission tomography/computed tomography (PET/CT) scans and endoscopic ultrasound. Patients received RT with 48 Gy to gross tumor and 43.2 Gy to elective nodal area in simultaneous integrated boost method divided in 24 fractions. Weekly platinum-based chemotherapy was administered concurrently. Side effects were evaluated using CTCAE v4. Images of 2-fluoro-2-deoxyglucose PET/CT before and after NACCRT were registered to planning CT images to create a region of interest for dosimetry parameters that spatially matched RP-related regions, including V10, V20, V50%, V27, and V30. Correlation between bio-physic parameters and toxicity was used to establish a constraint model for avoiding RP.ResultsAmong the investigated cohort, clinical downstaging, complete pathological response, and 5-year overall survival rates were 59.6%, 40%, and 34.4%, respectively. Multivariate logistic regression analysis demonstrated that each individual set standardized uptake value ratios (SUVRs), neither pre- nor post-NACCRT, was not predictive. Interestingly, cutoff increments of 6.2% and 8.9% in SUVRs (delta-SUVR) in registered V20 and V27 regions were powerful predictors for acute and chronic RP, respectively.ConclusionSpatial registration of metabolic and planning CT images with delta-radiomics analysis using fore-and-aft image sets can establish a unique bio-physic prediction model for avoiding RP in esophageal cancer patients receiving NACCRT.

Efficacy of Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in ER-positive Breast Cancer: Results From a Prospective Institutional Database

BackgroundAlthough neoadjuvant chemotherapy (NACT) has been established as a standard for medically fit patients with locally advanced breast cancer, there has been renewed interest in utilizing neoadjuvant endocrine therapy (NET) for women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Rates of pathologic complete response (pCR) are known to be low, but data regarding down-staging and long-term outcomes are inconsistent. Patients and MethodsA prospective institutional database of patients with breast cancer treated with neoadjuvant therapy from 2012 to 2017 was analyzed to identify patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Patients who received NET were compared with those who received NACT. A matched analysis (age, stage, grade) was performed to compare rates of down-staging, pCR, breast conserving surgery, and CPS+EG scores. ResultsA total of 176 patients met eligibility criteria. Of these, 111 (63%) patients received NACT, 51 (29%) received NET, and 14 (8%) received both sequentially. Women prescribed NET were older (65.5 vs. 51.2 years; P < .0001) and presented with lower clinical stage (P < .0001). The median duration of NET was 90 days. When matched, clinical down-staging was more frequent with NACT (20/51; 39%) compared with NET (11/51; 22%) (P = .032). Of these, 2% achieved pCR in each cohort. Conversion rates to breast conserving surgery eligibility were low (8% and 13% with NET and NACT; P = .70). No significant differences in CPS+EG scores were identified. ConclusionsSignificantly higher rates of down-staging were achieved with NACT compared with NET when patients were matched. This study highlights the importance of establishing tumor biology and the need for biomarkers that can be used as predictive tools to inform treatment.

Clinical downstaging and quality of life after neoadjuvant chemotherapy in patients with locally advanced rectal cancer: Interim analysis from a phase II clinical trial.

e15178 Background: The role of neoadjuvant FOLFOX in achieving clinical downstaging and improvement in quality of life (QOL) in patients with locally advanced rectal cancer (LARC) remains to be established. We are conducting a phase II prospective clinical trial to evaluate the use of six cycles of FOLFOX as neoadjuvant chemotherapy in patients with T2-T3/N0-N+ rectal cancer. We now report tumor clinical downstaging and patient-reported QOL in our first patient cohort. Methods: Eleven Patients enrolled in our phase II prospective trial. Patients received three months of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) administered every two weeks. After three weeks of recovery, each patient was treated with conventional chemo-radiotherapy (5FU or capecitabine) All patients had an MRI and endorectal ultrasound at baseline and after completion of FOLFOX. A compilation of validated QOL questionnaires were also administered before and after FOLFOX. Results: A total of 11 patients completed the chemotherapy regimen. Based on pelvic MRI, complete clinical response (T0N0) was achieved by seven patients (64%), one patient (9%) was clinically downstaged but three (27%) didn’t have any changes following FOLFOX. Importantly, we found no disease progression during the FOLFOX course. QOL assessment after FOLFOX regimen showed trend towards improvement in general health, mobility, bladder control and psychological health. These changes in QOL were not statistically significant due to the small sample size. Patients self-grading of their general health before starting FOLFOX was 50% compared to 75% after. Of the five patients with pain at time of diagnosis, four reported complete pain relief while the fifth reported improvement from extreme to moderate pain. Three patients reported improvement in their anxiety/depression. In terms of bowel function, although there was trend towards improvement in the urgency subscale, other bowel functions subscales were unchanged. In general, scores for mobility, selfcare, and bladder function were slightly better after FOLFOX. Conclusions: This study suggests that adding only six cycles of neoadjuvant FOLFOX before CRT not only resulted in clinical downstaging of (LARC) but showed a trend toward improved QOL. This result provides some reassurance for oncologists that this approach does not diminish QOL with no risk of disease progression during the time of neoadjuvant chemotherapy. These findings need to be validated in a larger phase III trial.

CLO19-023: Induction Chemotherapy Followed by Chemoradiation and Trans-Anal Full Thickness Local Excision or Total Mesorectal Resection in Patients With T2-T3/NO-N+ Adenocarcinoma of the Rectum; Preliminary Results of Phase 2 Prospective Clinical Trial

Background: The National Comprehensive Cancer Network (NCCN) Guidelines recently recognized total neoadjuvant therapy (TNT) as an acceptable option in patients with T3 and any N rectal cancer. Previous studies suggested that patients who received chemotherapy prior to conventional preoperative chemoradiation (CRT) and surgery allowed patients to receive more of their planned treatment with a better toxicity profile and increase in pathological response. However, those studies used a long course of FOLFOX or used capecitabine and oxaliplatin as an induction regimen. We are conducting a phase 2 prospective clinical trial to evaluate the use of 6 cycles of FOLFOX as TNT in patients with T2-T3/N0-N+. Patients and Methods: Patients with T2-T3/N0-N+ enrolled on our phase 2 prospective trial were included for this analysis. Patients received 6 cycles of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin), which was administered every 2 weeks. After 3 weeks of recovery period, patients then received conventional CRT with 5FU or capecitabine. All patients got MRI and endorectal ultrasound (ERUS) at baseline, after completing FOLFOX 3-months regimen and after finishing conventional CRT. Patients underwent either full-thickness local excision or total mesorectal resection depending on their tumor response to neoadjuvant therapy. The time interval between completion of radiation therapy and surgery ranged between 7and 12 weeks. Results: A total of 10 patients completed the chemotherapy and CRT treatment regimen. 9 patients proceeded to surgery and the 10th patient is scheduled for surgery. Clinical downstaging by MRI or ERUS was shown in 9 of 10 patients with only 6 cycles of FOLFOX. Complete clinical response was achieved in 6 patients as evident by ERUS/MRI of the pelvis after 3 months of FOLFOX before CRT. Complete pathological response was found in 4 of 9 patients (44%). In addition, 4 other patients had significant albeit not complete pathological response. Conclusions: This study suggests that adding only 6 cycles of neoadjuvant FOLFOX before CRT improved clinical and pathological downstaging of T2-T3/N0-N+ rectal adenocarcinoma and may facilitate organ preservation surgery. This is strategy needs to be investigated in larger phase III trials to validate these findings.

Improving early detection of breast cancer in sub-Saharan Africa: why mammography may not be the way forward

Background and methodsThe prevention and control of breast cancer in sub-Saharan Africa (SSA) is an increasingly critical public health issue. Breast cancer is the most frequent female cancer in SSA and mortality rates from this disease are the highest globally. Breast cancer has traditionally been considered a disease of high-income countries, and programs for early detection have been developed and implemented in these settings. However, screening programs for breast cancer in SSA have been less effective than in high-income countries. This article reviews the literature on breast cancer in SSA, focusing on early detection practices. It then examines the case for and against mammography and other early detection approaches for breast cancer in SSA.ResultsWomen with breast cancer in SSA are younger compared with high-income countries. Most women present with advanced disease and because treatment options are limited, have poor prognoses. Delay between symptom onset and healthcare seeking is common. Engagement with early detection practices such as mammography and breast examination is low and contributes to late stage at diagnosis.DiscussionWhile early detection of breast cancer through screening has contributed to important reductions in mortality in many high-income countries, most countries in SSA have not been able to implement and sustain screening programs due to financial, logistical and sociocultural constraints. Mammography is widely used in high-income countries but has several limitations in SSA and is likely to have a higher harm-to-benefit ratio. Breast self-examination and clinical breast examination are alternative early detection methods which are more widely used by women in SSA compared with mammography, and are less resource intensive. An alternative approach to breast cancer screening programs for SSA is clinical downstaging, where the focus is on detecting breast cancer earlier in symptomatic women. Evidence demonstrates effectiveness of clinical downstaging among women presenting with late stage disease.ConclusionsApproaches for early detection of breast cancer in SSA need to be context-specific. While screening programs with mammography have been effective in high-income countries, evidence suggests that other strategies might be equally important in reducing mortality from breast cancer, particularly in low-resource settings. There is a strong argument for further research into the feasability and acceptability of clinical downstaging for the control of breast cancer in SSA.

Glutathione S-transferase Pi 1 is a valuable predictor for cancer drug resistance in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S‐transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. Proliferation of GSTP1 knockdown cells was significantly decreased (P < .01), and the frequency of early apoptosis was increased (P < .05). Invasion capacity of GSTP1 knockdown cells was slightly decreased in transwell assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were carried out. Viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (P < .01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells was markedly increased over that of control cells by cisplatin exposure (P < .01). In immunohistochemistry assay of resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (P = .02). In summary, GSTP1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients.

Two-Phased Strategy for Improvement of Breast Cancer Care in Bangladesh

Purpose Bangladesh has a low incidence of breast cancer; however, the incidence is rising rapidly and the mortality rate is significantly higher, which is complicated by limited resources. Hence, a screening and treatment strategy will not be the same as those of high-income countries. Methods We did a literature review, resource evaluation, and finally propose a resource-stratified two-phased implementation strategy to improve breast cancer care in Bangladesh. Results There is a lack of qualitative and quantitative epidemiologic data. According to limited available data, breast cancer demography is different, as almost all patients present in advanced stage and most are premenopausal women. We have identified the three most important factors that affect breast cancer management: social, cultural, and religious barriers to early detection; few treatment facilities, which are concentrated mainly in the capital; and a lack of female health care providers while seeking treatment. We propose a two-phased approach. A female-orientated primary health care system has been successful in Bangladesh in achieving many health goals. In the first phase, we propose involving a female health assistant of the primary health care system to increase awareness, early detection (clinical downstaging), and effective referral of patients with breast cancer. This program can be integrated into existing perinatal care, as a majority of patients with breast cancer are of reproductive age. At the same time, we will modify tertiary health care (THC) to establish a model one-stop breast cancer facility and we propose a single day of a week when female health care providers will be available to provide care. THC providers will conduct outreach programs at the district level. In addition, a population-based epidemiologic study and cancer registry should be started immediately. In the second phase, we aim to establish an effective breast cancer care facility at the secondary health care level, as this is accessible by a large portion of the population. We propose establishing a one-stop breast cancer facility in every district that will be inspired by the THC model clinic. Adequate resources should be allocated to achieve this goal. Conclusion This strategy could be a model for other resource-limited developing countries. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . No COIs from the authors.

Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy.

This is the largest study to date evaluating response rates and pathologic complete response (pCR) and predictors thereof, based on molecular subtype, in women with breast cancer having undergone neoadjuvant chemotherapy (NC). The National Cancer Database was queried for women with cT1-4N1-3M0 breast cancer having received NC. Patients were divided into four subtypes: luminal A, luminal B, Her2, or triple negative (TN). Multivariable logistic regression ascertained factors associated with developing pCR. Kaplan-Meier analysis evaluated overall survival (OS) between patients by degree of response to NC when stratifying patients by subtype. Of a total of 13,939 women, 322 (2%) were luminal A, 5941 (43%) luminal B, 2274 (16%) Her2, and 5402 (39%) TN. Overall, 19% of all patients achieved pCR, the lowest in luminal A (0.3%) and the highest in Her2 (38.7%). Molecular subtype was an independent predictor of both pCR and OS in this population. Clinical downstaging was associated with improved survival, mostly in women with luminal B, Her2, and TN subtypes. Subgroup analysis of the pCR population demonstrated 5-year OS in the luminal B, Her2, and TN cohorts of 93.0, 94.2, and 90.6%, respectively (Her2 vs. TN, p = 0.016). Assessing nearly 14,000 women from a contemporary United States database, this is the largest known study examining the relationship between response to NC and molecular subtype. Women with luminal A disease are the least likely to undergo pCR, with the highest rates in Her2 disease. Degree of response is associated with OS, especially in luminal B, Her2, and TN patients. Despite the comparatively higher likelihood of achieving pCR in TN cases, this subgroup may still experience a survival detriment, which has implications for an ongoing national randomized trial.