Organ Preservation In Patients Research Articles

Association of Lateral Pelvic Lymph Nodes with Disease Recurrence and Organ Preservation in Patients with Distal Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy.

Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer. Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate. A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management. We analyzed the association of visible LLN (LLN+), LLN≥7mm (short axis) on baseline MRI, and LLN≥4mm on restaging MRI with recurrence, metastasis, and rectum preservation. At baseline, 57 out of 324 (18%) patients had LLN+. In 30 (53%) of 57 patients with LLN+ on baseline MRI, the LLN disappeared after TNT. Disease recurrence in LLN was rare (3.5% of patients with LLN+ and 0.4% of patients with LLN-). All patients with recurrence in LLN also had distant metastasis. The rate of organ preservation was significantly lower in patients with LLN≥4mm on restaging MRI (P=0.013). We found no significant differences in rates of local recurrence or metastasis between patients with LLN+ vs. LLN- and in patients with LLN≥7 vs.<7mm on baseline MRI. LLN dissection was performed in 3 patients; 2 of them died of distant metastasis. LLN involvement is not associated with disease recurrence or metastasis, but persistence of LLN≥4mm after TNT is negatively associated with rectum preservation in patients with locally advanced rectal cancer treated with TNT. Dissection of lateral nodes likely benefits few patients.

Assessing the OPRA trial for surgical oncologists: Safety and feasibility of a total neoadjuvant therapy approach in patients with rectal cancer

The Organ Preservation in patients with Rectal Adenocarcinoma (OPRA) trial is a randomized, non-blinded, phase II prospective study that investigated total neoadjuvant therapy (TNT) and a selective “watch-and-wait” (WW) approach in locally advanced rectal cancer (LARC). It compared two TNT regimens: induction chemotherapy-chemoradiotherapy (INCT-CRT) and chemoradiotherapy-consolidation chemotherapy (CRT-CNCT). Depending on tumor response, patients were offered WW or surgery. The primary endpoint was disease-free survival (DFS), hypothesizing that patients who underwent TNT with selective WW would have improved DFS compared to historical rates. Secondary endpoints included organ preservation (OP) and overall survival, hypothesizing that differences between INCT-CRT and CRT-CNCT could indicate a superior regimen. Results demonstrated treatment of LARC with TNT and selective WW allows for OP in approximately half of patients without negatively impacting oncologic outcomes such as DFS. The data show that a CRT-CNCT regimen had higher rates of OP, lower rates of tumor regrowth, and similar DFS compared to INCT-CRT. Lastly, DFS does not differ between patients who undergo immediate TME versus TME after regrowth. Thus, patients treated with TNT who achieve a clinical complete response (cCR) can safely undergo WW with the potential for OP. Current research to improve TNT and enhance cCR will expand the utility of the WW approach, including the intensification of neoadjuvant chemotherapy (Janus trial), comparing short-course and long-course CRT prior to CNCT (ENSEMBLE and German trials), utilizing fluoropyrimidine-chemotherapy with and without oxaliplatin in the context of WW (CHOW trial), and exploring less invasive operative approaches for early-stage tumors (NEO and NEO-RT trials). SynopsisThe OPRA trial demonstrates treatment of locally advanced rectal cancer using total neoadjuvant therapy with selective “watch-and-wait” allows organ preservation in approximately half of patients without negatively impacting oncologic outcomes. For widespread adoption of “watch-and-wait”, data from accruing prospective trials are needed to demonstrate its viability across diverse clinical settings.

Locally Advanced Rectal Cancer: New Neoadjuvant Strategies and Total Neoadjuvant Therapy

Treatment strategies for locally advanced rectal cancer are changing significantly. The treatment recommended in German guidelines for locally advanced tumors of neoadjuvant radio(chemo)therapy (RChT), followed by surgery and, if necessary, adjuvant therapy, are increasingly be abandoned in favor of the following concepts: (i) prolonged neoadjuvant therapy (i.e. "more chemotherapy before resection", referred to as total neoadjuvant therapy, TNT); (ii) organ preservation in patients with a complete clinical response after neoadjuvant radiochemotherapy. (iii) omission of radiotherapy in tumors with a low risk of local recurrence; (iv) definitive treatment with immunotherapy (checkpoint inhibitors) for patients with a primary harboring microsatellite instability (MSI). Herein, current strategies and study concepts are to be discussed based on the guideline-based status quo.

Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy

Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment. To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade. This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023. Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP. OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test. There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival. In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT. ClinicalTrials.gov Identifier: NCT02008656.

Indian clinical practice consensus guidelines for the management of oral cavity cancer: Update 2022

The treatment of oral cavity cancer primarily depends on the location, tumor size, and feasibility of organ preservation in patients with negative margins. A liquid biopsy is a minimally invasive approach for detecting blood-based signatures such as circulating tumor cells (CTCs) and circulatory tumor DNA (ctDNA). To assess the presence of occult metastatic disease, sentinel lymph node biopsy (SLNB) is recommended in early-stage oral cavity cancer (OCC). In India, surgery is the preferred choice of treatment for oral cancers. Selected patients, who are medically inoperable or refuse surgery, should be given definitive radiotherapy (RT) as an alternative to surgery. Concurrent chemoradiation (CCRT) may be considered an alternative option to definitive RT in patients with unresectable oral cancer.

Which tumour factors preclude organ preservation in patients with rectal cancer?

BackgroundcT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes, extramural vascular invasion (EMVI) and mesorectal fascia threatening (MRF+) have been utilized as exclusion criteria in several studies on the watch-and-wait (w&w) strategy. Here, our aim was to validate these criteria through a post hoc analysis of two pooled prospective studies on w&w following routine radio(chemo)therapy. MethodsA review of baseline magnetic resonance imaging was performed in a subgroup of 223 patients treated at a single institution. Of these, 17.9 % started w&w, 12.6 % achieved clinical complete response (cCR) and 9.0 % sustained cCR during median follow-up of 54 months. ResultsThe multivariable logistic analysis showed that the proportion of circumferential bowel involvement and EMVI significantly influenced the chance of sustained cCR; odds ratios were 0.063 (95 % confidence interval [CI] 0.008–0.489, p = 0.008), and 0.109 (95 % CI 0.014–0.850, p = 0.034), respectively. Sustained cCR was observed in none of the 57 patients with 90 %–100 % circumferential bowel involvement and in only one of the 89 patients with EMVI. In contrast, cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes or MRF+ were not independently associated with sustained cCR. Among the subgroups of patients with these features but without (near-)circular tumour or EMVI+, sustained cCR was observed in 12 %–25 % of patients. ConclusionSustained cCR after routine preoperative radio(chemo)therapy is unlikely in patients with (near-)circular tumour or EMVI, whereas patients with cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes and MRF+ should not be denied w&w.

Optimisation of Organ Preservation treatment strategies in patients with rectal cancer with a good clinical response after neoadjuvant (chemo)radiotherapy: Additional contact X-ray brachytherapy versus eXtending the observation period and local excision (OPAXX) — protocol for two multicentre, parallel, single-arm, phase II studies

IntroductionStandard treatment for patients with intermediate or locally advanced rectal cancer is (chemo)radiotherapy followed by total mesorectal excision (TME) surgery. In recent years, organ preservation aiming at improving quality of...

Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Squamous Cell Carcinoma Esophagus: Demographics and Evaluation of Prognostic Factors at a Tertiary Care Center in India.

Neoadjuvant chemoradiation followed by surgery has been the standard of care for locally advanced carcinoma esophagus. We present our experience and inference of various factors associated with the same treatment and the prognostic influence of the same. A retrospective analysis of a cohort of 132 squamous cell carcinoma esophagus patients post neoadjuvant chemoradiation operated with curative intentwas carried out. The 2-year overall survival rate was 64.5%. A pathological complete response was achieved in 32.5% of patients and was the only factor that significantly determined overall survival (p = 0.048). Neoadjuvant chemoradiation before surgery for locally advanced squamous cell cancer of the esophagus remains the standard of care with a pathological complete response being a significant factor in predicting overall survival. More prospective randomized studies are necessary to analyze factors affecting and predicting a pathological complete response which would help organ preservation in patients with a complete response.

Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Locally Advanced Laryngeal/Hypopharyngeal Carcinoma: Preliminary Results of INSIGHT Study

Previous studies have demonstrated excellent pathological response of induction PD-1 inhibitor with chemotherapy for locally advanced head and neck cancer. To our knowledge, there is scarce evidence on induction chemotherapy (ICT) and PD-1 inhibitor in organ preservation for patients (pts) with laryngeal/hypopharyngeal carcinoma. Hence, the aim of this study is to evaluate the efficacy and toxicities of ICT and PD-1inhibitor (Toripalimab) followed by radiotherapy or surgery, for pts with resectable locally advanced laryngeal/hypopharyngeal carcinoma. This isa single-arm phase II study. Pts with histopathologic confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and ECOG PS 0-1 were eligible. Three cycles of ICT (paclitaxel 175 mg/m d1, cisplatin 25 mg/m d1-3) combined with PD-1 inhibitor (Toripalimab 240 mg d0) were given. Response assessment (RECIST 1.1) was performed post-ICT. Patients with complete response (CR)/partial response (PR) of primary tumor received concurrent chemoradiation, followed by maintenance therapy of Toripalimab for eight cycles. Otherwise, patients were referred to surgery, followed by adjuvant radiation (RT)/chemoradiation (CRT), and then maintenance therapy of Toripalimab. The primary endpoint is larynx-preservation (LP) rate at 3 months post-RT. Forty-two patients were planned. Based on a two-stage Fleming design (one-sided α:10%, power: 80%), if at least 22 patients attained LP of the first 27 patients in stage I or at least thirty-two pts attained LP of the 42 patients at the end of stage II, the null hypothesis would be rejected. The cohort would enroll 15 more pts in stage II if 19-21 pts in stage I observed LP, and the study would be terminated if the number of pts with LP were less than 18 in stage I. A total of 27 pts were enrolled. By the cut-off date Feb 8, 2023, all reached at least 3 months of follow-up post-RT. Median age was 63 (53-74) years with 92.6% male. Hypopharyngeal cancer accounted for 66.7%. There were 74.1% who were T3 to T4, and 77.7% were N2 to N3. Six cases had primary invasion of esophagus and five pts underwent pretreatment tracheostomy. ORR of ICT was 85.2%. Afterward, 21 pts were treated with concurrent CRT, while 6 pts received surgery of primary tumor. At 3 months post-RT, 23 pts attained organ preservation and the LP rate was 85.2%. With a median follow-up of 13.5 months, 1-year OS rate, PFS rate and LP survival rate was 83.1%, 79.5% and 79.4%, respectively. During ICT, 22.2% of pts experienced grade 3-4 treatment-related AEs (TRAEs). The most common grade 3-4 TRAEs were nausea and neutrophil count decreased. The primary endpoint LP rate was met. In this cohort of extensive locally advanced laryngeal/hypopharyngeal carcinoma, ICT and Toripalimab followed by radiotherapy or surgery resulted in satisfactory short-term LP rate and encouraging survival.

Induction chemotherapy and toripalimab for larynx preservation in resectable locally advanced laryngeal/hypopharyngeal carcinoma: Preliminary results of INSIGHT study.

6068 Background: Previous studies have demonstrated excellent pathological response of induction PD-1 inhibitor with chemotherapy for locally advanced head and neck cancer. To our knowledge, there is scarce evidence on induction chemotherapy (ICT) and PD-1 inhibitor in organ preservation for patients (pts) with laryngeal/hypopharyngeal carcinoma. Hence, the aim of this study is to evaluate the efficacy and toxicities of ICT and PD-1 inhibitor (Toripalimab) followed by radiotherapy or surgery, for pts with resectable locally advanced laryngeal/hypopharyngeal carcinoma. Methods: This is a single-arm phase II study. Pts with histopathologic confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and ECOG PS 0-1 were eligible. Three cycles of ICT (paclitaxel 175mg/m2 d1, cisplatin 25mg/m2 d1-3) combined with PD-1 inhibitor (Toripalimab 240mg d0) were given. Response assessment (RECIST 1.1) was performed post-ICT. Pts with complete response (CR)/partial response (PR) of primary tumor received concurrent chemoradiation, followed by maintenance therapy of Toripalimab for eight cycles. Otherwise, pts were referred to surgery, followed by adjuvant radiation (RT)/chemoradiation (CRT), and then maintenance therapy of Toripalimab. The primary endpoint is larynx-preservation (LP) rate at 3 months post-RT. Forty-two pts were planned. Based on a two-stage Fleming design (one-sided α:10%, power: 80%), if at least 22 pts attained LP of the first 27 pts in stage I or at least 32 pts attained LP of the 42 pts at the end of stage II, the null hypothesis would be rejected. The cohort would enroll 15 more pts in stage II if 19-21 pts in stage I observed LP, and the study would be terminated if the number of pts with LP were less than 18 in stage I. Results: A total of 27 pts were enrolled. By the cut-off date Feb 8th, 2023, all reached at least 3 months of follow-up post-RT. Median age was 63 (53-74) years with 92.6% male. Hypopharyngeal cancer accounted for 66.7%. 74.1% were T3 to T4, and 77.7% were N2 to N3. Six cases had primary invasion of esophagus and five pts underwent pretreatment tracheostomy. ORR of ICT was 85.2%. Afterwards, 21 pts were treated with concurrent CRT, while 6 pts received surgery of primary tumor. At 3 months post-RT, 23 pts attained organ preservation and the LP rate was 85.2%. With a median follow-up of 13.5 months, 1-year OS rate, PFS rate and LP survival rate was 83.1%, 79.5% and 79.4%, respectively. During ICT, 22.2% of pts experienced grade 3-4 treatment-related AEs (TRAEs). The most common grade 3-4 TRAEs were nausea and neutrophil count decreased. Conclusions: The primary endpoint LP rate was met. In this cohort of extensive locally advanced laryngeal/hypopharyngeal carcinoma, ICT and Toripalimab followed by radiotherapy or surgery resulted in satisfactory short-term LP rate and encouraging survival. Clinical trial information: NCT04995120 .

Sustained organ preservation in patients with rectal cancer treated with total neoadjuvant therapy: Long-term results of the OPRA trial.

3520 Background: The preliminary results of the OPRA trial demonstrated that a substantial number of patients with locally advanced rectal cancer treated with total neoadjuvant therapy (TNT) could achieve organ preservation. Although most tumor regrowths seem to occur within the first 3 years, longer follow-up is needed to assess the ongoing risk of regrowth. Here, we report the long-term organ preservation rate and oncologic outcomes of the OPRA trial. Methods: A prospective, multi-institutional phase II trial, in which patients with stage II or III rectal cancer were randomized to receive either induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients underwent reassessment for treatment response 8-12 weeks after TNT. Patients who achieved a complete or near-complete response after finishing TNT were offered a watch and wait approach (WW). Those with incomplete response were recommended total mesorectal excision (TME). We report 5-year disease-free survival (DFS), organ preservation (defined as TME-free survival), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) for each treatment group. We also compared DFS between patients who underwent upfront TME after restaging and patients who underwent TME after tumor regrowth. All analyses followed the intention-to-treat principle and groups were compared using the log-rank test. Results: Of the 324 patients randomized, 158 were assigned to the INCT-CRT group and 166 to the CRT-CNCT group. Median follow-up was 56 months; 85 DFS events were observed. The rates of 3- and 5-year DFS, TME-free survival, LRFS, DMFS and OS are listed in the Table. In total, 80 of the 225 (36%) patients who started WW developed a regrowth; 94% occurred within 2 years and 99% occurred within 3 years. The rate of TME-free survival at 5 years was significantly higher for CRT-CNCT (54%) than in INCT-CRT (39%). 5-year DFS was similar for patients who underwent TME after restaging (61%) compared to patients who underwent TME after regrowth (62%, p = 0.86). Conclusions: In patients with rectal cancer treated with TNT and WW, the majority of tumor regrowths occur in the first 2 years, and regrowth after 3 years is vanishingly rare. Salvage TME for tumor regrowth during WW appears to offer similar outcome to immediate TME after incomplete response to TNT. Distant metastases remain the most frequent cause of treatment failure, with similar rates in the two treatment groups. Clinical trial information: NCT02008656 . [Table: see text]

Is RAPIDO too rapid for rectal cancer?

Is RAPIDO too rapid for rectal cancer?

Radiotherapy, atezolizumab, and bevacizumab in rectal cancers with the aim of organ preservation: The TARZAN study.

158 Background: Rectal cancer is traditionally treated with total mesorectal excision (TME), with/without neoadjuvant radiotherapy (RT) and chemotherapy. This approach often leads to temporary or permanent colostomies and other long-term morbidity such as urinary and sexual dysfunction in over 60% of patients. Organ preservation is increasingly being pursued in patients with a clinical complete response (cCR) following neoadjuvant treatment, thereby aiming to avoid TME-surgery. Based on preclinical data suggesting immunomodulatory effects of RT, and the synergy of combined PD-L1/VEGF blockade in several tumor types, the TARZAN study (NCT04017455) combines these treatments aiming to increase chances of organ preservation in patients with mainly MMR proficient (pMMR) rectal cancer without the need for chemotherapy. Methods: Patients with clinical stage ≤T3ab N0-1 distal-mid rectal tumors without mesorectal fascia involvement underwent 5x5 Gy RT followed by 3 cycles of atezolizumab and bevacizumab. Response was evaluated by MRI and endoscopy. The primary endpoint was clinical complete and near-complete response (CR) rate at 12 weeks after RT. Secondary endpoints included safety, organ preservation, pathologic (near) CR in case of surgery, and relapse free survival. According to a Simon’s 2-stage design, ≥3 responders were needed in stage I (18 patients) to continue accrual into stage II. Here we report data from stage I. Results: Eighteen patients (14 male, median age 63), all with pMMR tumors, were treated. Six tumors were cN1 on MRI, 10/18 tumors were ≥4cm and for 10/18 patients abdominoperineal resection (APR) appeared necessary due to distal tumor location. At the time of response evaluation, (near-)CR was achieved in 10/18 (56%) patients according to the primary endpoint. With a median follow-up of 20 months, 9/18 (50%) patients remain without TME surgery. Of these 9 patients, 5 underwent local excision to achieve organ preservation and in 5 patients no additional intervention was needed (cCR). The remaining 9 patients underwent TME surgery (4 APR), and pathologic assessment revealed near-CR in two patients, and a pCR in one patient. Three patients developed distant recurrences, one in the organ-sparing group. Neoadjuvant treatment was well-tolerated with grade 3 study drug-related adverse events (AEs) in 1 (5%) patient. Grade 3 surgery-related AEs occurred in 5/9 (55%) patients, including 4 anastomotic leaks and 1 abscess. Conclusions: Neoadjuvant RT followed by atezolizumab and bevacizumab resulted in a promising rate of clinical (near-)CRs in 56% of patients without the need for chemotherapy, reaching the primary endpoint. Accrual is ongoing in stage II, in which an additional 20 patients will be treated. Clinical trial information: NCT04017455 .

Feasibility of circulating tumor DNA (ctDNA) to guide organ preservation in patients with node-negative rectal cancer undergoing neoadjuvant chemotherapy, excision, and observation in the phase II CCTG CO.28 trial.

180 Background: CCTG CO.28 evaluated 3 months of neoadjuvant CAPOX or FOLFOX followed by transanal excision surgery (TES) in patients (pts) with T1-T3, N0 rectal cancers with the goal of organ preservation. Total mesorectal excision (TME) was recommended for inadequate downstaging or high-risk features on TES pathology. Detection of ctDNA is associated with a high rate of recurrence in high risk resected colorectal cancer. However, the sensitivity of ctDNA in early-stage rectal cancer is unclear. Methods: Tissue CGP was performed retrospectively on pretreatment resected tumor using Foundation OneCDx (F1CDx), followed by MRD detection using FoundationOneTracker. Briefly, variants were selected from F1CDx using an algorithm that filters out non-tumor derived variants (e.g. germline). A tumor-informed personalized multiplex PCR-next generation sequencing assay, consisting of up to 16 variants, was used to detect ctDNA and quantify plasma mean variant allelic frequency (VAF) and mean tumor molecules per mL of plasma (MTM/mL). FoundationOneTracker was performed on blood samples collected pre/post-neoadjuvant chemotherapy. Buffy coat sequencing was performed at FMI to validate the monitoring variant selection algorithm. Results: 52 pts underwent F1CDx and FoundationOneTracker analysis. KRAS mutations were observed in 60% (n =31) of cases; MSI-H and BRAF V600E mutations were not detected. From 1,580 distinct variants detected in tissue and paired buffy coat sequencing, 985 had VAF &gt;30% in the buffy coat specimen and were considered germline. The variant selection algorithm filtered 99.8% (n = 983) of germline variants; the remaining 2 were not selected for primer design. A median of 7 variants (range 2-16) were tracked per pt. Detectable ctDNA was found in 0% (0/6), 19% (6/32) and 55% (6/11) of treatment naïve T1, T2 and T3ab cases, respectively, and 83% of those which were initially positive (10/12) cleared ctDNA post chemotherapy. Three pts had detectable ctDNA pre-excision, including 1 who was negative pretreatment. From 42 pts with pre/post-treatment plasma, 19 pts were recommended for TME; 2 had detectable ctDNA, 5 had ctDNA clearance, and 12 had no ctDNA detection. Conclusions: Node-negative rectal cancer exhibited ctDNA shed in a minority of pts, with most clearing ctDNA on chemotherapy before their TES. The dynamic ctDNA signal we demonstrate could supplement clinical factors in informing organ preservation in very early-stage rectal cancer. Larger studies are needed to determine if this information can be used to personalize therapy. Clinical trial information: NCT03259035 . [Table: see text]

Inhibiting TGF-β to increase response rates to chemoradiotherapy in rectal cancer.

With the rapid increase in the incidence of rectal cancer in young adults, 1 Bailey CE Hu CY You YN et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975–2010. JAMA Surg. 2015; 150: 17-22 Crossref PubMed Scopus (528) Google Scholar interest in organ preservation as an oncologically safe 2 Garcia-Aguilar J Patil S Gollub MJ et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol. 2022; (published online April 28.)https://doi.org/10.1200/JCO.22.00032 Crossref PubMed Scopus (28) Google Scholar , 3 Smith JJ Strombom P Chow OS et al. Assessment of a watch-and-wait strategy for rectal cancer in patients with a complete response after neoadjuvant therapy. JAMA Oncol. 2019; 5: e185896 Crossref PubMed Scopus (208) Google Scholar and cost-effective strategy to improve patients' quality of life has also been growing. 4 Miller JA Wang H Chang DT Pollom EL Cost-effectiveness and quality-adjusted survival of watch and wait after complete response to chemoradiotherapy for rectal cancer. J Natl Cancer Inst. 2020; 112: 792-801 Crossref PubMed Scopus (12) Google Scholar Studies evaluating novel radiosensitisers in rectal cancer are receiving attention as a consequence of the need to develop personalised treatment strategies to increase response rates while also facilitating organ preservation. The TGF-β pathway has intrigued scientists and clinicians for decades, 5 Barnard JA Beauchamp RD Coffey RJ Moses HL Regulation of intestinal epithelial cell growth by transforming growth factor type beta. Proc Natl Acad Sci USA. 1989; 86: 1578-1582 Crossref PubMed Scopus (316) Google Scholar and targeting this complex signalling network has now been implicated as a potential way to improve response to radiotherapy. 6 Batlle E Massagué J Transforming growth factor-β signaling in immunity and cancer. Immunity. 2019; 50: 924-940 Summary Full Text Full Text PDF PubMed Scopus (781) Google Scholar However, decades of research into TGF-β inhibitors—both as a monotherapy and in combination with radiotherapy—have shown mixed clinical efficacy, probably due to the complex biology of TGF-β and the context-dependent effects of its inhibition. 6 Batlle E Massagué J Transforming growth factor-β signaling in immunity and cancer. Immunity. 2019; 50: 924-940 Summary Full Text Full Text PDF PubMed Scopus (781) Google Scholar , 7 Andarawewa KL Paupert J Pal A Barcellos-Hoff MH New rationales for using TGFbeta inhibitors in radiotherapy. Int J Radiat Biol. 2007; 83: 803-811 Crossref PubMed Scopus (58) Google Scholar Chest CT scan plus x-ray versus chest x-ray for the follow-up of completely resected non-small-cell lung cancer (IFCT-0302): a multicentre, open-label, randomised, phase 3 trialThe addition of thoracic CT scans during follow-up, which included clinic visits and chest x-rays after surgery, did not result in longer survival among patients with NSCLC. However, it did enable the detection of more cases of early recurrence and second primary lung cancer, which are more amenable to curative-intent treatment, supporting the use of CT-based follow-up, especially in countries where lung cancer screening is already implemented, alongside with other supportive measures. Full-Text PDF

Clinical and radiological predictors of organ preservation in patients with rectal cancer treated with total neoadjuvant therapy.

3619 Background: Baseline rectal MRI is routinely used for tumor staging, selecting the initial treatment and prognostication of patients with rectal adenocarcinoma. However, associations of baseline clinical and MRI variables with organ preservation (OP) in a prospective randomized trial have not been reported. Methods: Patients with MRI staged clinical stage II or III rectal adenocarcinoma treated in a prospective phase II clinical trial were randomized to either induction chemotherapy (FOLFOX or CAPEOX) followed by chemoradiation or chemoradiation followed by consolidation chemotherapy (FOLFOX or CAPEOX) and recommended total mesorectal excision (TME) or watch-and-wait (WW) based on clinical response. The primary outcome was OP, defined as the time from randomization to the clinical decision of TME or last follow-up, whichever occurred first. Clinical variables included: age, sex, race, tumor grade, radiation dose and treatment arm. Radiological variables (evaluated by baseline MRI prior to randomization) included: distance from the anal verge, tumor length, clinical T stage, clinical N stage, relationship to the mesorectal fascia, presence of extramural vascular invasion (EMVI) and mucinous radiographic findings (&gt;50%). Associations of OP with clinical and radiological variables were assessed utilizing the Cox regression model in univariate and multivariate settings. The final multivariate model was chosen using backward selection. Results were analyzed by intention to treat. Results: Case report forms (CRFs) from baseline MRI were available for 289 of 324 randomized patients (89%). Patients with CRFs differed from those without CRFs in race, distance of the tumor from the anal verge and clinical T stage. Median follow-up was 3.4 years. A total of 156 of 324 patients were recommended TME during the study period. The 3-year OP rate was 47%. Independent predictors of OP in the multivariate analysis can be seen in the table. Conclusions: Although the patients included in this analysis may not be fully representative of the entire cohort, our data shows that several radiological variables associated with unfavorable tumor biology – tumor involvement of the mesorectal fascia, presence of EMVI and involved mesorectal nodes – were negatively associated with organ preservation. This information will be useful in selecting rectal cancer patients for WW and should be used for patient stratification in future clinical trials. Clinical trial information: NCT02008656. [Table: see text]

A141 IS SURGERY STILL THE ONLY TREATMENT OPTION FOR CURABLE RECTAL CANCER?

BackgroundRectal cancer is curable by standard surgery with Total Mesorectal Excision (TME). However, there are well known associated long-term bowel and sexual dysfunctions. Non-operative management (NOM) is an emerging treatment for patients with operable rectal cancer. There is evidence supporting dose response for tumor control in rectal adenocarcinoma.AimsIn the era of modern technologies, Image-guided adaptive endorectal brachytherapy is a means to deliver local radiotherapy boost treatments. We explored its role in a randomized phase II/III trial (NCT03051464) for patients aiming to achieve cure without surgery. Total Mesorectal Excision (TME) free survival at 2 years was the primary endpoint. We now present the interim analysis upon accrual of the first 40 patients.MethodsIn randomized trial, patients with operable cT2-3ab N0 M0 rectal cancer received 45 Gy in 25 fractions of pelvic external beam radiotherapy (EBRT) with concurrent 5-FU/ Capecitabine. They were randomized to receive either an EBRT boost of 9 Gy in 5 fractions (Arm A), or three weekly adaptive brachytherapy boosts for a total of 30 Gy in 3 fractions (Arm B).ResultsForty patients were included (20 per arm). The median age was 66 years; baseline characteristics were well balanced in terms of age, tumor location, T stage and tumor size (Table 1). The acute treatment related toxicities are similar as shown in table 2 but in arm B, there were two deaths: one patient died during his chemotherapy and external beam treatment from congestive heart failure and one patient from a heart attack after treatment prior to salvage TME surgery. The proportion of complete clinical response was 50% (n=10/20) in Arm A and 90% in Arm B (n=18/20). With a median follow-up of 2.2 years, local regrowth at 2 years occurred in 4/10 patients (40%) in Arm A and 4/18 patients (22%) in Arm B. TME-free survival rate at 2 years was 45.9% in Arm A and 85.1% in Arm B (p=0.0036) (Figure 1).ConclusionsThe interim analysis of this trial suggests that these two strategies of radiation dose escalation are feasible and lead to high chances of organ preservation in patients with operable rectal cancer. The Independent Monitoring Comittee (IDMC) approved the continuation of patient recruitment in the phase III study as planned. Funding AgenciesElekta

Trauma Surgeons' Perceptions of Resuscitating Lethally Injured Patients for Organ Preservation.

Trauma surgeons face a challenge when deciding whether to resuscitate lethally injured patients whose organ donor status is unknown. Data suggests practice pattern variability in this setting, but little is known about why. We conducted semi-structured interviews with trauma surgeons practicing in Level 1 or 2 trauma centers in Tennessee. Interviews focused on ethical dilemmas and resource constraints. Analysis was performed using inductive thematic analysis. Response rate was 73% (11/15). Four key themes emerged. All described resuscitating patients to buy time to collect more definitive clinical information and to identify family. Some acknowledged this served the secondary purpose of organ preservation. 11/11 participants felt a primacy of obligation to the patient in front of them even after it became apparent, they could not personally benefit. For 9/11 (82%), the moral obligation to consider organ preservation was secondary/balancing; 2/11 (18%) felt it was irrelevant/immoral. Resource allocation was commonly considered. All participants expressed some limitation to resources they would allocate. All participants conveyed clear moral agency in determining resuscitation extent when the goal was to save the patient's life, however this was less clear when resuscitating for organ preservation. Across themes, perceptions of a "standard practice" existed but the described practices were not consistent across interviewees. Widely ranging perceptions regarding ethical and resource considerations underlie practices resuscitating toward organ preservation. Common themes suggest a lack of consensus. Despite expressed beliefs, there is no identifiable standard of practice amongst trauma surgeons resuscitating in this setting.

Multidisciplinary treatment strategy for early rectal cancer

The early rectal cancer (ERC) has increased with the national cancer screening project for early detection of colorectal cancer. The gold standard treatment for low rectal cancer is low anterior resection (LAR) based on total mesorectal excision. However, radical resection results in a high mortality and complication rate, and the deterioration of quality of life due to LAR syndrome, genitourinary dysfunction, and possible permanent stoma. Local excision with chemoradiation therapy could be one of the alternative therapeutic strategies for the organ preservation and a cure of cancer. To decide the treatment strategies, it is important to establish sophisticated indications that can maximize the therapeutic effect. ERC has heterogeneous pathological features, including aggressive behavior and occult lymph node metastasis, with different responses to chemoradiotherapy. Therefore, radiologic, endoscopic and pathologic evaluation to predict the risk of lymph node metastasis and local recurrence has been evolving to determine the optimal treatment strategy in the patient-tailored medicine. Recently, the long-term outcomes of prospective randomized clinical trials provide new hope for organ preservation in patients with ERC. In this paper, we aim to review various risk factors related to local recurrence and discuss the optimal treatment strategy for ERC.

Clinical Significance of Endoscopic Response Evaluation to Predict the Distribution of Residual Tumor after Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

To appropriately adopt the organ preservation approach, including subsequent chemoradiotherapy (CRT) in patients who respond to neoadjuvant chemotherapy (NAC), the distribution of residual disease, including pathological lymph nodes (LNs) and recurrence site, needs to be recognized preoperatively. This study was designed to evaluate whether endoscopic response evaluation can predict residual tumor distribution. Patients with esophageal squamous cell carcinoma who underwent transthoracic esophagectomy (TTE) were retrospectively reviewed. Endoscopic responder (ER) to NAC was defined according to primary tumor endoscopic findings. Recurrence-free survival (RFS), overall survival (OS), and residual tumor patterns were compared between groups. Of 193 patients, 40 (20%) were classified as ER. ERs showed significantly better RFS and OS. The pN location was found within the primary tumor and cN field in 88% of ERs, which was significantly higher than non-ERs at 63% (p = 0.004). Furthermore, the postoperative recurrence incidence in the distant organ was significantly lower in the ERs than the non-ERs (8%, 32%, respectively, p = 0.002). Residual disease, including postoperative initial recurrence, existed within the same field as the primary tumor and cN in 88% of ERs, significantly higher than 42% in the non-ERs (p < 0.001). Endoscopic response evaluation can preoperatively predict distribution of residual tumors after NAC, which could help radiation field selection in subsequent definitive CRT when patients prefer to omit TTE. Along with improvements in NAC response rate, this could facilitate organ preservation in patients who respond to NAC.