Clinical Complete Response Rate Research Articles

PD-1/PD-L1 inhibitors for early and middle stage microsatellite high-instability and stable colorectal cancer: a review.

Programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important immune checkpoint molecules that contribute to tumor immune evasion. However, the main treatment modalities for patients with early and intermediate stage colorectal cancer (CRC) are surgery, and the role of PD-1/PD-L1 inhibitors in these patients is not yet clear. Therefore, this study aims to review the treatment progress of PD-1/PD-L1 inhibitors for early- and intermediate-stage microsatellite high-instability (MSI-H) and stable (MSS) colorectal cancer, in order to provide more options for patients with early- and intermediate-stage colorectal cancer. A scoping review of clinical trial registries ( Clinicaltrials.gov and EU clinical trial registers) and PubMed/Medline database of trials on PD-1/PD-L1 Inhibitors for early and middle-stage MSI-H and MSS CRC was done up to March 2024. A total of 19 trials related to early to mid-stage MSH-I or MSS CRC were included. Among them, 6 trials are in recruiting status, 3 trials are in active, not recruiting status, 3 trials are completed, 1 trial is terminated, and 1 trial is unknown. Of these, 9 trials involve MSI-H type CRC, and 10 trials involve MSS type CRC. Preclinical phase I/II trials are predominant, with only 3 clinical phase III trials. In trials related to MSI-H type CRC, 4 studies involve PD-1/PD-L1 inhibitors combined with neoadjuvant therapy, and 5 studies involve combination therapy. In trials related to MSS type CRC, 3 studies involve PD-1/PD-L1 inhibitors combined with targeted therapy, 2 studies involve PD-1/PD-L1 inhibitors combined with chemotherapy, 1 study involves PD-1/PD-L1 inhibitor combined immunotherapy, 1 study involves PD-1/PD-L1 inhibitors combined with bacterial therapy, and 3 studies involve PD-1/PD-L1 inhibitors combined with comprehensive therapy. As for primary outcome measures, 4 trials select pathological complete response rates, 3 trials select progression-free survival rate, 3 trials select objective response rate, 3 trials select overall survival rate, 4 trials select disease-free survival rate, 1 trial selects clinical complete response rate, and 1 trial selects percentage of participants with a dose-limiting toxicity. For early- and middle-stage MSI-H and MSS CRC, PD-1/PD-L1 inhibitors have shown some therapeutic efficacy, as evidenced by phase I/II studies. However, contemporary trial designs exhibit heterogeneity, with relatively few inclusion criteria, the use of various drug combinations and regimens, and significant variations in reported endpoints. Nevertheless, more double-arm, multicenter, randomized controlled trials are still needed to confirm the efficacy of immunotherapy.

Efficacy and safety of bevacizumab in neoadjuvant and concurrent chemoradiotherapy for refractory cervical cancer patients.

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

Abstract PO1-22-08: Ductal Lavage versus Oral Corticosteroids in Patients with Idiopathic Granulomatous Mastitis: A Multicenter, Open-label, Randomized, Controlled, Non-inferiority Study

Abstract Background: Idiopathic granulomatous mastitis (IGM) is an inflammatory breast disease characterized by the presence of mass, erythema and fistula. Various treatments have been proposed, including steroids, surgery, immunosuppressants, and observation alone. However, most of the reported studies are single-center, retrospective, single-arm with limited sample sizes, leaving the optimal treatment strategy unknown. In a previous single-arm study, we reported the efficacy and safety of ductal lavage as a novel treatment. This presentation presents the results of a multicenter, open-label, randomized controlled, non-inferiority trial that compares the efficacy and safety of ductal lavage with oral corticosteroids as the first-line treatment for IGM patients. Methods: Eligible IGM patients were randomized 1:1 to receive either ductal lavage or oral corticosteroids, stratified by M-score status. The M-score quantitatively evaluates IGM symptom severity as reported in our previous studies. Ductal lavage involved the intraductal infusion of lidocaine, triamcinolone acetonide, and ceftriaxone with saline, a total 5 times within 2 weeks. Oral corticosteroids were administered using prednisone or methylprednisolone at an initial dose of 20-40mg per day, decreased by 5mg every 2 weeks, and then maintained at 20mg per day for at least 1 month. The primary outcome was the rate of complete Clinical Response (cCR), which was defined as achieving M-score≤1 during any follow-up visit. Secondary outcomes included median time to first cCR, treatment failure, relapse, adverse events, and protocol compliance rate. If the lower limit of 95%CI of the absolute difference between ductal lavage and oral corticosteroids was greater than -15%, the non-inferiority was met. This trial was approved by the ethical committee of Sun Yat-sen Memorial Hospital and registered with ClinicalTrials.gov (NCT03724903). Results: Recruitment for this trial began in March 2019 and follow-up ended in May 2023 at 3 hospitals in China. In the intention-to-treat set (N=140), 69 patients were randomly assigned to the ductal lavage group and 71 patients to the oral corticosteroids group. The cCR rates after treatment were 85.51% (95% CI 77.20 ~ 93.81%) and 87.32% (95% CI 79.59 ~ 95.06%) in the ductal lavage and oral corticosteroids groups, respectively. The rate difference was -1.82% (95% CI -13.17 ~ 9.54%), not exceeding the non-inferiority margin (Non-inferiority P=0.011). In the per-protocol set (N=111), the cCR rate difference was -5.32%(ductal lavage: 92.86% vs. oral corticosteroids: 98.18%),with a 95%CI of -12.94% to 2.29%,also not exceeding the non-inferiority margin(Non-inferiority P=0.006).No significant differences were observed between groups in median time to first cCR (34.0 vs. 32.5 days, P= 0.878), treatment failure rate (14.49% vs. 11.27%, P=0.569), or relapse rate (10.14% vs. 4.23%, P=0.302).In the safety analysis set (N=129), the most frequently reported adverse events ( >15%) in the ductal lavage group were irregular menstruation (46.27%), while in the oral corticosteroids group, they were Cushingoid (79.03%), epigastric pain (17.74%), and arthralgia (16.13%). Conclusions: Ductal lavage demonstrates non-inferiority to oral corticosteroids in terms of efficacy as a first-line treatment for IGM patients. Furthermore, ductal lavage exhibits a significantly favorable adverse events profile. Primary endpoint in ITT and PP set *P value for non-inferiority comparison. Secondary endpoint in PP set §P value calculated by chi-square test. Adverse event in safety set No adverse event exceeding Grade3 have been recorded. Citation Format: Kai Chen, Xiaolin Chen, Shunrong Li, Liling Zhu, Jian Zhang, Tingting Hu, Hui Huang, Heng Huang, Lili Chen, Qiaozhen Xiao, Linhong Su. Ductal Lavage versus Oral Corticosteroids in Patients with Idiopathic Granulomatous Mastitis: A Multicenter, Open-label, Randomized, Controlled, Non-inferiority Study [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 PO1-22-08.

Efficacy and Safety of Neoadjuvant Subcutaneous Envafolimab in dMMR/MSI-H Locally Advanced Colon Cancer.

Neoadjuvant immunotherapy with programmed death-ligand 1 blockade for colon cancer, especially for mismatch repair-deficient (dMMR)/high microsatellite instability (MSI-H) colon cancer, has gained considerable attention recently. This study aimed to assess the safety and efficacy of neoadjuvant subcutaneous envafolimab in patients with dMMR/MSI-H locally advanced colon cancer. Patients with dMMR/MSI-H locally advanced colon cancer treated with envafolimab at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital from October 2021 to July 2023 were retrospectively reviewed and analyzed. The primary endpoint was the pathological complete response (CR) rate, and secondary endpoints were treatment-related adverse events and complete clinical response rate. Overall, 15 patients were analyzed. After neoadjuvant immunotherapy with envafolimab, six patients achieved a CR, with five partial responses, and four stable disease. Three patients achieving a complete clinical response chose to accept a "watch and wait" strategy, and surgery was performed in 12 patients. Postoperative pathology results revealed seven patients achieved pathological CRs, and five patients achieved tumor regression grade 2, with 66.7% of the total CR rate. The most common treatment-related adverse events were pruritus and rash (40%), with no severe cases. No recurrences occurred over a 7.9-month follow-up. Envafolimab yielded promising surgical outcomes and safety in dMMR/MSI-H locally advanced colon cancer, representing a promising treatment modality for this population.

Effect of neoadjuvant concurrent three-dimensional conformal chemoradiotherapy with conventional two-dimensional chemoradiotherapy in locally advanced rectal cancer

Background: Rectal carcinoma is a prevalent clinical condition, and treatment hinges on factors like tumor specifics, staging, grading, and histopathological characteristics. While surgery remains the primary treatment, neoadjuvant chemoradiotherapy, particularly using 3D-CRT, has proven effective in reducing local recurrence rates for locally advanced cases. Alternatively, 2D-RT is considered for neoadjuvant treatment. This study aimed to compare the impact of neoadjuvant concurrent three-dimensional conformal chemoradiotherapy with conventional two-dimensional chemoradiotherapy in the context of locally advanced rectal cancer. Methods: In this multicentre quasi-experimental study, 60 patients with biopsy-proven adenocarcinoma and clinically confirmed locally advanced rectal cancer, were divided into Group A (receiving oral capecitabine with three-dimensional conformal radiotherapy) and Group B (receiving the same capecitabine dose with 50 Gy two-dimensional radiotherapy). After surgery within 6-12 weeks, outcomes were analysed. Results: After neoadjuvant chemoradiotherapy, clinical complete response rates were 16.7% in Group A and 10.0% in Group B, with a higher pathological complete response in Group A (10.0% vs. 3.3%). Tumor downsizing occurred in 83.3% of Group A and 73.3% of Group B, and sphincter-sparing surgery was achieved in 73.3% of Group A and 56.7% of Group B. Grade 2 toxicities included anemia (10.0% vs. 13.3%), leucopenia (13.3% vs. 20.0%), diarrhoea (10.0% vs. 16.7%), proctitis (13.3% vs. 40.0%), and urinary toxicity (10.0% vs. 20.0%). Grade-1 toxicities were nausea (20.0% vs. 40.0%), vomiting (20.0% vs. 36.7%), mucositis (56.7% vs. 60.0%), hand-foot syndrome (33.3% vs. 40.0%), and urinary toxicity (43.3% vs. 56.67%), with significant proctitis in Group A (p=0.012). Other toxicities showed non-significant p-values (>0.05). Conclusions: Tumour response was not statistically significant between the patients of concurrent 3D-CRT and 2D-RT Arms. But the patients of 3D-CRT arm showed better response arithmetically. Also, there was an observable significant reduction of toxicities (lower gastrointestinal) in the 3D-CRT arm.

Organ preservation in locally advanced colorectal cancer with microsatellite instability-high after immunotherapy

Neoadjuvant immunotherapy has achieved exciting efficacy with high clinical complete response (cCR) and pathologic complete response (pCR) rates and durable long-term effects. PD-1 checkpoint blockade-based immunotherapy has been highly successful in microsatellite instability high (MSI-H)/mismatch repair deficiency (dMMR) colorectal cancer and has been recommended as the first-line treatment for metastatic colorectal cancer by domestic and international guidelines. Several studies have shown that immunotherapy can be a potentially curable treatment for MSI-H rectal cancer and has even shown promise in organ preservation in colon cancer. In this study, we first clarified the feasibility of the watch-and-wait strategy after PD-1 checkpoint blockade treatment by indirect and direct evidence. Then from the assessment tools (including digital rectal examination, endoscopy, radiology, and lymph node assessment), the viable assessment methods of cCR for immunotherapy and related difficulties are proposed. Finally, the medication choices of immunotherapy, the treatment regimen, and the follow-up strategy are further discussed. We hope that neoadjuvant immunotherapy could be appropriately applied in MSI-H/dMMR colorectal cancer so that more patients can achieve organ preservation.

Abstract 4025: A phase II trial of neoadjuvant gemcitabine, cisplatin plus tislelizumab followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Clinical efficacy, safety and the biomarker analysis

Abstract Immune checkpoint inhibitors (ICIs) have been widely used in recurrent or metastatic nasopharyngeal carcinoma (NPC), but the addition of ICIs to chemoradiotherapy in locoregionally advanced (LA) NPC requires further investigation. We conducted a phase II, single-arm trial to evaluate the efficacy and safety of neoadjuvant gemcitabine, cisplatin (GP) plus tislelizumab followed by concurrent chemoradiotherapy (CCRT) in LA-NPC. All participants received 3 cycles of GP chemotherapy plus tislelizumab (200 mg) followed by 3 cycles of cisplatin-based CCRT. The primary endpoint was the clinical complete response rate (CR) after neoadjuvant chemoimmunotherapy (NAT). The secondary endpoints include pathological CR rate, progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), etc. Pretreatment blood samples and paired (pre-/post-NAT) tissue biopsies were collected to perform full-spectrum peripheral T-cell profiling, PD-L1 and tertiary lymphoid structures (TLS) staining. Among all 63 participants, the CR rate after NAT reached 41.3% (95% CI, 28.8%-53.8%), far exceeding our hypothesized CR rate of 22%. The objective response rate (ORR) and pCR rate after NAT were 88.9% (95% CI, 80.9% to 96.9%) and 74.6% (95% CI, 62.1% to 84.7%), respectively. As of July 15th, 2023, after the median follow-up of 25 months, the 2-year PFS and OS were 98.4% and 100%. The incidence of grade 3-4 immunotherapy-related adverse events was 1.6%. The compliance of CCRT was not compromised. Patients who achieved CR had significantly more circulating CD4+ and CD8+ effector memory T cells (Tem), regulatory T cells (Treg) and follicular helper T cells (Tfh). The peripheral abundance of LAG3+ Tem and Tfh were independently predictive of NAT response. The number and maturation of TLS significantly increased after NAT in the CR group, but not in the Non-CR group. GP chemotherapy plus tislelizumab followed by CCRT was highly therapeutic and safe in treating LA-NPC, further randomized phase III studies are awaited. Citation Format: Xiao-Yun Li, Si-Yi Xie, Qiu-Yan Chen, Hai-Qiang Mai, Lin-Quan Tang. A phase II trial of neoadjuvant gemcitabine, cisplatin plus tislelizumab followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Clinical efficacy, safety and the biomarker analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4025.

Predictive role of ctDNA in esophageal squamous cell carcinoma receiving definitive chemoradiotherapy combined with toripalimab

The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy.

The Role of Level III Dissection in Locally Advanced Breast Cancer following Neoadjuvant Chemotherapy—A Prospective Study

Breast cancer is the most common female cancer in India, with a significant number presenting as locally advanced breast cancer (LABC). Level III clearance is routinely performed in our institute in LABC following neoadjuvant chemotherapy (NACT). In our previous retrospective study, level III positivity rate was 15.5%. We aim to prospectively assess level III positivity rate in LABC patients post-NACT. This is a prospective study of female patients with LABC (defined as cT3N1–3M0 or cT4N0–3M0 or cTanyN2,3M0) who received NACT and underwent surgery including level III dissection from November 2019 to October 2021. Data collected included age, menopausal status, TNM stage at presentation, grade, hormone receptor and HER2 status, treatment response, ycT and ycN stage, and final histopathology. Univariate and multivariate analysis was undertaken. p-Value less than or equal to 0.05 was considered significant. Study recruited 598 patients. Level III node positivity rate was 8.4%. The clinical complete response rate (cCR) was 36% (215/598). On univariate analysis, significant association was present between level III node and cCR (p < 0.01), ycT0 stage (p = 0.001), ycN0 stage (p = 0.028), level II node positivity (p = 0.001), ypT stage (p = 0.001), and ypN stage (p = 0.001). On multivariate analysis, significant association was present between level III node and ycT stage (p < 0.001), ypT stage (p = 0.001), and ypN stage (p = 0.001). Level III positivity rate in LABC post-NACT is high. In patients with advanced ycT stage, it would be advisable to offer complete axillary dissection including level III. Level III dissection may be avoided in patients with ycT0 or ycN0 or with cCR.

An online rectal cancer tumoroid biorepository: A resource to facilitate multimodal data integration.

159 Background: Advancing genetic and computational technologies have increased the complexity and quantity of data available in the field of rectal cancer research. As such, there is a need for a centralized source of data to aid and organize current research efforts. To this end, our team has created a unique online biorepository of rectal cancer tumoroids which may serve as a resource for a community of researchers. Methods: The rectal cancer tumoroid biorepository was created in cBioPortal in 2015. Organoids were derived from patient tumor samples (tumoroids). These samples represented multiple treatment timepoints and included primary, recurrent, and metastatic tumors. These tumoroids were further analyzed by various assays such as MSK-IMPACT and IC50 (to fluorouracil, FOLFOX, and FOLFIRI) to obtain patient-specific genomic and chemosensitivity data. A tumoroid profile was then created in cBioPortal for each sample. Clinical information was collected by chart review and annotated into the tumoroid profiles using the unique features of cBioPortal. These included interactive filters and graphical depictions of patient demographics, clinical and pathologic staging, treatment course, clinical response, overall survival, and disease-free survival. Results were organized in an intuitive visual display for convenient analysis. Novel features such as chemosensitivity plots and an interactive patient timeline were incorporated as well. Results: In total, 401 rectal cancer tumoroids have been derived from 177 unique patients. Approximately 32% of the tumoroids were from patients 50 years or younger, and 63% of patients have a treatment naïve sample in our repository. Ten percent of tumoroids were derived from T1-T2 tumors, 56% from T3 tumors, and 17% from T4 tumors. Additionally, 14% of tumoroids were derived from primary tumor recurrences while 6% were derived from metastases. Of the 78% of tumoroids with completely annotated clinical data, 8% were MSI-H, 11% were clinical complete responders, and 5.5% were pathologic complete responders. Lastly, complete IC50 data with clinical correlates has been established for 20% of tumoroids. These data show that tumoroids with a high sensitivity to chemotherapy (FOLFOX) correlated with a 3.3-fold increase in clinical complete response rates in the corresponding patients (p=0.0263). Conclusions: Integrating histopathological, clinicogenomic, and tumoroid response data, this expanding online resource provides a platform to identify valid biomarkers for patient treatment response. This publicly available biorepository built within cBioPortal is intuitive and flexible to accommodate and organize a wide range of data and has the potential to serve as an important resource in rectal cancer research.

Ezabenlimab (BI 754091) plus modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) followed by chemoradiotherapy (CRT) in patients (pts) with stage III squamous cell anal carcinoma (SCCA): Early efficacy endpoint results from the phase II INTERACT-ION study.

2 Background: CRT is the standard of care for locally advanced SCCA. However, up to 50% of pts experience recurrence/definitive colostomy; there is an unmet need for novel treatment (Tx) options to improve pt outcomes. mDCF is a standard first-line Tx for advanced SCCA, and anti-programmed death protein-1 (PD-1) immunotherapy has been shown to be effective in a subset of chemorefractory SCCA. Preclinical and clinical data support the feasibility and the potential of combining mDCF with anti-PD-1 immunotherapy. Methods: INTERACT-ION (NCT04719988) is an open-label, single-arm study in pts with Tx-naïve Stage III (T4N0 or TxN+) SCCA to evaluate ezabenlimab (anti-PD-1 antibody) plus mDCF as induction therapy, followed by CRT and then maintenance with ezabenlimab. Pts received induction ezabenlimab (240 mg intravenously, every 3 weeks, 3 cycles) plus mDCF (D [40 mg/m2], C [40 mg/m2] on Day 1; F [1200 mg/m2/day for 2 days] every 2 weeks, 4 cycles). If there was no disease progression after 2 months, pts received an additional cycle of ezabenlimab plus 2 cycles of mDCF. Planned early efficacy endpoint analyses were performed after 2 months of Tx. Pts with radiological objective response (OR; RECIST v1.1), pathological (p) complete response (CR)/near CR (<10% viable tumor cells) by repeat biopsy, and molecular CR (undetectable human papillomavirus [HPV] circulating tumor DNA) by liquid biopsy, received involved nodetumor bed CRT with intensity-modulated radiation therapy (IMRT) followed by 7 cycles of ezabenlimab. All other pts received standard IMRT based-CRT. The primary endpoint is the clinical CR rate 10 months after Cycle 1 of ezabenlimab plus mDCF. Results: At analysis cut-off date,43 pts had been enrolled; 37 pts had preliminary early efficacy endpoint evaluation. All but 1 pt (97.3%) received the planned 4 cycles of ezabenlimab plus mDCF prior to evaluation; 1 pt presented with treatment-related capillary leak syndrome after Cycle 1 and died of a lung infection 3 months later. Radiological assessment was performed in 33 pts; 32 (97.0%) had radiological OR including 14 (42.4%) with CR. One HPV- pt had disease progression. Pathological response data were available for 21 pts; 16 (76.2%) had pCR/near pCR. For molecular response, 3 pts were HPV- (excluded). Among 23 HPV+ evaluable pts, 21 (91.3%) had a molecular CR. Two pts had a significant decrease at 2 months (decrease: 14/1 and 54/1); then molecular CR after radiotherapy. No safety signals were identified by an independent safety review committee. Conclusions: Preliminary results from this ongoing Phase II study show promising antitumor activity and manageable safety of ezabenlimab plus mDCF in pts with Tx-naïve, locally advanced SCCA. Further evaluation of this new treatment regimen is warranted. Clinical trial information: NCT04719988 .

Quality of life and clinical outcomes in rectal cancer patients treated on a 1.5T MR-Linac within the MOMENTUM study

Background and purposeThis study assessed quality of life (QoL) and clinical outcomes in rectal cancer patients treated with magnetic resonance (MR) guided short-course radiation therapy (SCRT) on a 1.5 Tesla (T) MR-Linac during the first 12 months after treatment. Materials and methodsRectal cancer patients treated with 25 Gy SCRT in five fractions with curative intent in the Netherlands (2019–2022) were identified in MOMENTUM (NCT04075305). Toxicity (CTCAE v5) and QoL (EORTC QLQ-C30 and -CR29) was primarily analyzed in patients without metastatic disease (M0) and no other therapies after SCRT. Patients who underwent tumor resection were censored from surgery. A generalized linear mixed-model was used to investigate clinically meaningful (≥10) and significant (P < 0.05) QoL changes. Clinical and pathological complete response (cCR and pCR) rates were calculated in patients in whom response was documented. ResultsA total of 172 patients were included, of whom 112 patients were primarily analyzed. Acute and late radiation-induced high-grade toxicity were reported in one patient, respectively. CCR was observed in 8/64 patients (13 %), 14/37 patients (38 %) and 13/16 patients (91 %) at three, six and twelve months; pCR was observed in 3/69 (4 %) patients. After 12 months, diarrhea (mean difference [MD] −17.4 [95 % confidence interval [CI] −31.2 to −3.7]), blood and mucus in stool (MD −31.1 [95 % CI −46.4 to −15.8]), and anxiety (MD –22.4 [95 % CI −34.0 to −10.9]) were improved. ConclusionHigh-field MR-guided SCRT for the treatment of patients with rectal cancer is associated with improved disease-related symptom management and functioning one year after treatment.

Chemoradiotherapy for squamous cell carcinoma of the rectum: a retrospective propensity-score matched analysis

A lack of evidence-based data on the chemoradiotherapy (CRT) efficacy in patients with squamous cell carcinoma of the rectum (SCCR) makes further study of this topic extremely important.Aim: The aim of our research was to estimate the efficacy of CRT in patients with SCCR compared to the rectal adenocarcinoma and squamous cell carcinoma of the anal canal (SCCAC).Materials and methods: Our study was based on analysis of medical records of patients with ICD–X code C20 and ICD-O 8070 / 3, 8070 / 3.1, 80703 in a database from 2007 to 2020 obtained from the archive of Research Institute FSBI “N. N. Blokhin Cancer Research Center” of the Ministry of Health of Russia. We included patients with SCCR who received CRT as initial treatment into the experimental group. Groups with rectal adenocarcinoma and SCCAC were created using propensity-score matching 1:2 taking into account sex, age, the cN clinical stage, histological grade and tumor size. The main study endpoints were 3‑year overall survival (OS) and disease-free survival (DFS) rates, complete clinical response rate and complete clinical or pathological response rate at 6 months after CRT, local recurrence and distant metastases rates, surgery rate.Results: We included 15 patients in SCCR group and 30 patients in rectal adenocarcinoma group and SCCAC group each. There were no significant differences in parameters that could affect the prognosis. The complete clinical response was achieved in 7 (46.7 %) patients with SCCR versus 3 (10.0 %) patients with adenocarcinoma (p = 0.005) and 24 (80.0 %) patients with SCCAC (p = 0.005). The surgery rate was 26.6 % (4 patients) in SCCR group, 6.67 % (2 patients) in SCCAC group, 90 % (27 patients) in adenocarcinoma group (p &lt; 0.001). The recurrence rate was 26.7 % (4 patients) in SCCR group versus 10.0 % (3 patients) in adenocarcinoma group (p = 0.146) and 6.7 % (2 patients) in SCCAC group (p = 0.063). The metastases rate was 26.7 % (4 patients) in SCCR group, 26.7 % (8 patients) in adenocarcinoma group (p &gt; 0.99). In SCCAC group metastases were detected in 1 (3.3 %) patient, which was significantly different compared to the SCCR group (p = 0.019). Median follow up was 44 months. The 3‑year OS was 78.8 % in SCCR group versus 91.0 % in adenocarcinoma group (p = 0.675), and 86.3 % in SCCAC group (p = 0.953). The 3‑year OS in adenocarcinoma and SCCAC groups did not differ (p = 0.996). The 3‑year DFS was 34.7 % in SCCR group versus 55.6 % in adenocarcinoma group (p = 0.504) and 82.9 % in SCCAC group (p = 0.031). The 3‑year DFS differences in adenocarcinoma and SCCAC groups were significant (p = 0.041).Conclusions: We have obtained important data on the CRT comparative efficacy in patients with SCCR, SCCAC and rectal adenocarcinoma. The high complete clinical response rate in SCCR group makes it possible to consider the use of CRT as the main treatment method. Results of our research can be used to plan the treatment of patients with SCCR.

Gastric Radiotherapy in the UK – Current Practice and Opinion on Future Directions

Gastric radiotherapy (RT) is more commonly practiced in the US compared to the UK, where postoperative chemoradiotherapy (CRT) is reserved for selected high-risk patients, and preoperative CRT is not standard of care pending the results of phase 3 trials, TOPGEAR and CRITICSII. CRT for inoperable, non-metastatic gastric cancer is also not recommended in the UK, despite being listed in NCCN guidelines. Recent systematic review of definitive gastric CRT (dCRT) conducted by the authors found median overall survival of 11-26.4 months, clinical complete response rates of 8-45% and acceptable rates of ≥G3 toxicity, supporting further research. Given these promising findings and perceived low uptake of gastric RT in the UK, we set out to establish current UK practice, opinion and RT technique to inform the development of a UK gastric RT protocol and future clinical trials. A 19 question survey was developed. Following local ethical approval and pilot by 4 clinical oncologists, the final survey was distributed electronically on 13/12/22 to UK Consultant Clinical Oncologists specializing in esophago-gastric (OG) cancer. Responses were anonymous. Survey was closed 6/2/23 and data analyzed using JISC/spreadsheet software. A total of 43 clinicians completed the survey. For gastric cancer, 28.6%, 7.1% and 9.5% would agree/strongly agree with use of postoperative (postopRT), preoperative (preopRT) or definitive RT (dRT) respectively, compared to 26.2%, 45.2% and 46.6% for type III gastro-esophageal junction tumors. 93% had prescribed palliative gastric RT in the last 3 years compared to 40.5% postopRT, 16.7% dRT and 9.5% preopRT. Main reasons for infrequent use were; rarely indicated within standard UK practice 88.4%, lack of UK gastric RT protocol 53.5%, toxicity concerns 44.2%. 45Gy/25# was most commonly used for preopRT (66%) and postopRT (86%), and 50Gy/25# for dRT (58%). 96% use IMRT/VMAT, 85% CT simulation with IV/oral contrast, 69% gastric filling protocol and 54% 4DCT. When ranked out of 10 (1 = low 10 = high), clinician confidence in accurately delineating gastric volumes mean rank was 4.33 for postopRT, with 9% rating ≥8/10, and 4.52 for dCRT/preopRT with 17% rating ≥8/10. However, 48.8% were experienced in outlining upper abdominal nodes and 62.8% duodenum. 93% would find a detailed outlining protocol useful, 81.4% wanted some form of peer review, 76.7% a nodal atlas, and 74.4% a workshop with an expert. 77.6% would be supportive of a future clinical trial of dCRT, with 23.4% needing more supporting evidence. No-one would not support a future trial in this setting. Gastric RT is not often practiced in the UK, due to lacking evidence and toxicity concerns. Given the growing evidence and supportive OG community, it is time to consider a trial of dCRT in the UK, which must include detailed RT protocols, atlases and educational materials to improve clinician confidence and ensure good RT quality assurance.

Therapy with direct antiviral drugs in patients with HCVassociated cryoglobulinemic vasculitis – is it always possible to achieve complete clinical and immunological responses after the virus eradication?

Background. The use of direct acting antiviral drugs (DAАs) leads to the achievement of a stable virological response (SVR) in 95–100 % of patients with HCV-associated cryoglobulinemic vasculitis (HCV-CV). However, in some patients, despite the eradication of the virus, clinical and immunological markers of vasculitis still remain.The aim: to evaluate clinical and immunological responses in patients with HCV-CV in comparison with patients with "asymptomatic" HCV- associated cryoglobulinemia (HCV- СG) after achieving SVR with the help of DAАs with long-term dynamic observation (12 months).Patients and Methods: The study included 45 patients: 23 with HCV-CV and 22 with "asymptomatic" HCV-CG, who underwent antiviral therapy with DAAs. Clinical-immunological, virological data were evaluated: before treatment, 12 weeks (3 months) and 48 weeks (12 months) after the end of treatment.Results: After a course of DAAs, SVR was diagnosed in all 45 (100 % of patients). In patients with HCV-CV, an immunological response (complete and partial) was observed by week 12 (SVR12) – in 56.5 % and by week 48 (SVR48) – in 73.9 % patients. In 6 patients (26.1 %), the immunological response was not achieved by SVR48. The rate of complete and partial clinical response 12 weeks after the end of treatment at the SVR12 period in patients with HCV-CV was 65.2 %, to the time of SVR48 amounted to 78.3 % patients. In 5 (21.7 %) individual manifestations of CV persisted and/or relapsed. In patients with HCV-CG, the frequency of complete and partial immunological responses after DAAs therapy was 77.3 % – by SVR12 and 86.3 % – by SVR48, respectively. No response was observed in 3 patients and it was characterized by trace-level of cryoglobulinemia.Conclusion: In most patients with HCV-CV eradication of HCV with help of DAAs leads to the achievement of clinical and immunological remission of the disease. However, in 20 % of patients manifestations of HCV-CV persist / recur immediately after the end of treatment or later relapses are observed. Based on these observations, patients with HCV-CV, especially those with severe underlying skin and kidney disease, are required long-term monitoring after SVR is achieved.

Neoadjuvant chemoradiation therapy combined with immunotherapy for microsatellite stable ultra-low rectal cancer (CHOICE II): study protocol of a multicentre prospective randomised clinical trial

IntroductionNeoadjuvant chemoradiotherapy (nCRT) could bring tumour shrinking and downstaging and increase the probability of organ preservation for patients with low rectal cancer. But for ultra-low rectal cancer, there is little...

Predictors of successful outcome after adrenalectomy for unilateral primary aldosteronism.

Unilateral primary aldosteronism (UPA) is the most frequent surgically curable form of endocrine hypertension. Adrenalectomy is the cornerstone of treatment for UPA, but outcomes after surgery are variable. The cause of resistant hypertension after surgery is still a matter of debate. Our aim was to investigate cure rates after surgery and to evaluate preoperative factors that might influence the surgical outcome. Between 2000 and 2021, the charts of 71 Tunisian patients who underwent laparoscopic adrenalectomy for UPA were retrospectively reviewed. Preoperative medical records were collected and follow-up data (1-158 months) were registered. Antihypertensive medication doses were calculated using defined daily doses (DDD) and postoperative outcomes were assessed using the Primary Aldosteronism Surgical Outcome (PASO) criterion. Of 91 enrolled patients, 71 (59% women, mean age 46 years, median length of follow-up 21 months) were suitable for evaluation. Thirty-four patients (48%) had complete clinical success according to the PASO criteria. The most relevant factors associated with complete clinical success on univariate analysis were: absence of diabetes (p= 0.007), low body mass index (BMI) (p= 0.001), lower preoperative DDD (p= 0.01), preoperatively controlled blood pressure (p= 0.024), higher plasma aldosterone to renin ratio (ARR) (p= 0.001), adenoma subtyping (p <0.001) and aldosteronoma resolution score (ARS) (p= 0.002). Multivariate regression analysis showed that the major predictors of complete clinical success were absence of diabetes (OR: 5.205), a BMI < 30 (OR: 4.930), a plasma ARR > 332 (OR: 4.554) and an ARS ≥ 3 (OR: 2.056). Complete and partial clinical response rates were achieved in respectively 48 and 43% of cases. The main predictors of complete resolution of hypertension were absence of diabetes, low BMI, high plasma ARR and high ARS. Taking these factors into account may help identify patients at risk of persistent postoperative hypertension who may require long-term surveillance and medication.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma.

To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5days, P = 0.042) than in the MF group. The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC.

Clinical characteristics and pathologic complete response (pCR) rate after neoadjuvant chemotherapy in postpartum women with breast cancer

PurposeBreast cancer (BC) is currently the leading cause of death in women worldwide. Studies have confirmed that pregnancy is an independent factor affecting the survival of BC patients. BC found during pregnancy, lactation, or shortly after delivery is what we used to think of as pregnancy-associated breast cancer (PABC). The current expert definition of this concept is not uniform; however, there is growing evidence that postpartum breast cancer (PPBC) differs from other types of BC in terms of both biological features and prognosis, with a slightly different focus on diagnosis and treatment. With the increase of female reproductive age population and changes in fertility policies in China, patients with PPBC are receiving increasing attention. Here, we systematically analyzed the clinicopathological characteristics and chemotherapeutic response of patients with PPBC. We retrospectively analyzed the clinicopathological data, molecular subtypes, chemotherapy regimens, and pathological complete remission (pCR) rates of 1343 patients with non-metastatic BC at Harbin Medical University Cancer Hospital from January 1, 2012 to May 31, 2023. The categorical data were compared by chi-square test and Fisher exact test using logistic regression model. Predictor variables with P < 0.05 in the univariate analysis were included in the multivariate regression analysis to investigate the relationship between different age groups and pCR.ResultsA total of 714 patients were eligible for analysis in this study, and 667 patients had a history of pregnancy, 40 (5.6%) of whom were PPBC patients. When diagnosed with BC, patients with PPBC were younger, more likely to undergo breast-conserving surgery (BCS), and more likely to achieve pCR (P < 0.05). In molecular typing, human epidermal growth factor receptor 2 (HER-2)-positive and triple-negative breast cancer (TNBC) were more frequent. In the entire cohort, HER-2 expression and delivery status were independent predictors of pCR rates in BC patients after neoadjuvant chemotherapy (NAC).ConclusionOur findings suggest that postpartum status is an independent predictor of pCR attainment in BC patients. PPBC is more sensitive to chemotherapy than other patients.We need to pay more attention to this group and achieve individualized treatment, which will help us treat BC better and provide new targets and blueprints for our clinical therapy.

Top Colorectal Articles from 2021 to Inform Your Cancer Practice.

Multimodality treatment for locally advanced rectal cancer is the standard of care. Treatments include surgery, radiation, and chemotherapy, with medical therapies now being favored in the neoadjuvant setting. Various regimens continue to be studied and defined in prospective randomized trials. The PRODIGE 23 and RAPIDO trials showed improved disease-free survival and pathologic complete response rates for split chemotherapy/radiation treatment and short-course radiation with consolidation chemotherapy, respectively; both compared with traditional neoadjuvant long course chemoradiation, surgery, and adjuvant chemotherapy. Furthermore, new regimens are yielding a higher rate of complete clinical response, allowing for non-operative management. Circulating tumor DNA provides a potential novel option for monitoring response to treatment and rectal cancer surveillance. This manuscript summarizes some of the key clinical trials and studies that are defining clinical practice.