Wait Strategy Research Articles

Clinical feasibility of the therapeutic strategies total neoadjuvant therapy and "watch and wait" in the treatment of rectal cancer patients with recurrence after clinical complete response.

In recent years, total neoadjuvant therapy (TNT) has emerged as a new therapeutic strategy against advanced rectal cancer (RC). After administration of TNT, some patients show complete clinical response (cCR) to treatment however, disputes about the effects of TNT and the alternative treatment plans in case of recurrence after cCR still exist. A total of 100 patients were included in this paper. CR and non-CR was observed when these patients were administered with TNT at the First Affiliated Hospital of Dalian Medical University, China from May 2015 to June 2021. These patients received different chemotherapeutic regimens, with close monitoring and watch and wait (W&W) strategy being applied by a multidisciplinary team (MDT). According to treatment results, patients were divided into a cCR group and a non-cCR group; according to the recurrence during W&W, they were divided into a recurrence group and a no-local-recurrence group. This study analyzed the factors that may affect the prognosis, and summarized the surgery and treatment after recurrence. The TNT strategy was effective, and 85% of patients achieved local remission. However, W&W did not affect the survival time of CR patients, nor did it cause new distant metastasis due to local recurrence during the observation period (P > 0.05). However, for patients with positive CRM, we do not recommend W&W as the first choice of treatment (P < 0.05). (1) Whole-course neoadjuvant therapy was an effective treatment scheme for advanced mid-term rectal cancer. The total local reduction rate of this group of cases was 85.00%, meaning that 25 patients achieved CR. (2) W&W was safe and reliable, and CR patients could receive it as the preferred treatment. (3) CRM was an independent risk factor for local recurrence in CR patients. We do not recommend W&W as the preferred treatment for CR patients with positive CRM.

Hearing After Vestibular Schwannoma Surgery: Is It Preserved Forever?

Currently, it is possible to preserve the auditory nerve in a large number of cases, but the preservation of the hearing itself is unpredictable. Apart from wait and scan strategy and stereoradiotherapy, hearing after vestibular schwannoma surgery is considered to remain stable even in long-term follow-up. Twenty-eight patients had preserved hearing after retrosigmoid suboccipital microsurgery of the vestibular schwannoma between 2008 and 2014. A standard audiological protocol was performed together with an magnetic resonance imaging evaluation of the fluid content of the inner ear. The mean difference in pure-tone average between the direct and final postsurgical examination was 12.758 dB ( p = 2.5E - 06). The word recognition score deteriorated by 17.45% ( p = 0.03516). The mean American Academy of Otolaryngology-Head and Neck Surgery score on the second examination was 2.5, and that on the second examination was 3.111 ( p = 0.00483). There was no significant deterioration in the healthy ear.The signal intensity ratio in the basal turn of the cochlea increased by an average of 0.13 points ( p < 0.05).Patients with persistent tumor or nodular enhancement in the internal acoustic meatus deteriorated significantly in hearing according to the American Academy of Otolaryngology-Head and Neck Surgery scale compared with patients without any finding in the meatus ( p = 0.01299). There is a discrete but gradual deterioration of the hearing in the postoperative period. Hearing impairment is more pronounced in patients with a nodular process in the internal acoustic meatus, regardless of whether it is growth active. After surgery, the pathological content of the inner ear normalizes (evaluated on T2 magnetic resonance imaging sequences).

Nierenersatztherapie

The clinical indications for initiating acute renal replacement therapy (ARRT) include life-threatening refractory disturbances of electrolyte, acid-base and fluid balances as well as severe clinical symptoms of the uremic syndrome. In most other cases a watch and wait strategy is justified; however, a consistent (at least daily) re-evaluation is mandatory. In intensive care patients with persistent oliguria or anuria for > 72 h despite stable hemodynamics and adequate volume status, initiation of RRT should be considered even in the absence of urgent clinical indications. For continuous RRT the guidelines recommend a total effluent volume (dialysate plus filtrate) of 20–25 ml/kg body weight/h which usually requires a higher prescription of effluent volume. The treatment duration and frequency of intermittent RRT should primarily be tailored to the patients’ individual needs regarding fluid, electrolyte, and acid-base balances. Treatment sessions every 2 days will usually be sufficient to achieve adequate solute clearance. Basic prerequisites for attempts at weaning from ARRT are stable hemodynamics, adequate fluid, electrolyte, and acid-base statuses and a urine output of at least 500 ml/24 h or a positive response to a furosemide stress test. The successful recovery of kidney solute clearance can be demonstrated by performing an endogenous creatinine clearance or quantification of the kinetic estimated glomerular filtration rate (KeGFR).

Conflict-based search with D* lite algorithm for robot path planning in unknown dynamic environments

This study proposes a locally observable robot pathfinding algorithm, conflict-based search with D* lite (CBS-D*), to realize automatic and effective pathfinding in mixed environments with dynamic obstacles. This algorithm takes Manhattan distance as the heuristic function and extends the incremental search range from 1order to 3order neighbors. It presents a prejudgment mechanism of collision avoidance and investigates a wait and circuity strategy to promote pathfinding performance. Compared with the D* lite, the experimental results demonstrate that CBS-D* achieves a higher success rate and obstacle avoidance number, and a lower time step. By this collision avoidance mechanism, CBS-D* gives all successes in pathfinding in various dynamic environments, while D* lite may result in some failures. Specifically, CBS-D* has around 31% in the average success rate of pathfinding improved to D* lite in a 32 × 32 map. Furthermore, CBS-D* gives a superiority of self-adaptability and intelligence in unknown dynamic environments.

Transient Monosomy 7 Is a Rare Event in Young Children with SAMD9L Syndrome

Monosomy 7 and deletion 7q are among the most common chromosomal aberrations in pediatric myeloid malignancies and generally associated with an increased risk of rapid progression to advanced neoplasia, warranting allogeneic hematopoietic stem cell transplantation (HSCT). However, several cases of transient monosomy 7 and spontaneous hematologic recovery upon loss of monosomy 7 in young children have been described in the literature. In several cases, germline mutations in sterile alpha-motif domain-containing protein 9 (SAMD9) and SAMD9-like (SAMD9L), both located on chromosome 7q, have been identified. Gain of function (GOF) mutations in SAMD9 and SAMD9L cause phenotypically overlapping syndromes that predispose to pediatric myelodysplastic syndrome (MDS) and are associated with non-hematological anomalies and variable immunodeficiency. GOF SAMD9/9L mutations inhibit cell proliferation and reduce cell survival of hematopoietic stem and progenitor cells (HSPCs). This may exert strong selection pressure on HSPCs to acquire somatic aberrations that improve their competitive fitness. To no surprise, a distinctive feature of SAMD9/9L syndromes is their propensity for somatic genetic reversion, including somatic loss of function mutations in SAMD9/9L in cis, uniparental isodisomy 7q, and non-random loss of chromosome 7 or 7q of the mutant allele. Multiple hematopoietic subclones with clone-defining somatic mutations can exist in the bone marrow and their composition may change over time due to the exceptionally high plasticity of hematopoiesis in young children. Consequently, monosomy 7 may spontaneously disappear in young patients with SAMD9/9L syndromes. Earlier observations had suggested that somatic compensatory mutations may be more frequent in SAMD9L than in SAMD9 mutated patients. Here, we investigate the natural history of young children with SAMD9L syndrome and monosomy 7. We report on seven patients with SAMD9L syndrome and monosomy 7 presenting before the age of 5 years in whom an initial surveillance strategy was electively chosen rather than timely allogeneic HSCT. All patients presented with refractory cytopenia of childhood with monosomy 7 at a median age of 1.0 years (range: 0.4-3.1 years). Six patients had an additional non-hematologic phenotype, including prematurity (P2, P5), small for gestational age (P1, P2, P7), cerebellar atrophy and developmental delay (P1), bilateral cleft lip and palate (P2), macrocephaly (P3, P6), shorter thumbs (P6), and big eye bulbs and dystrophy (P7). Immunodeficiency was present in five patients ranging from hypogammaglobulinemia (P1, P2, P5, P6, P7) to B and NK cell deficiency patients (P2, P5, P6, P7). At a median follow-up of 35 months (range: 10-51 months), allogeneic HSCT had been employed in four patients for severe neutropenia and/or bacterial infection (P1, P7), persistence of monosomy 7 beyond the age of 5 years (P5) or disease progression to MDS with excess blasts (P2). One patient (P2) suffered transplant-related mortality, while the remaining patients were alive at last follow-up. Three patients did not require definitive treatment. Two of the three patients had complete loss of the monosomy 7 clone with concomitant recovery of blood counts (P4, P6), a third patient had normalized blood counts, but cytogenetic and molecular studies at follow-up were missing (P3). Secondary somatic mutations were detected in six patients. Five patients carried somatic SAMD9L mutations in cis (P2, P3, P4, P6, P7). Two patients with spontaneous loss of monosomy 7 carried large somatic SAMD9L subclones that were stable over time and presumably maintained hematopoiesis (P4, P6). In addition, two patients carried somatic mutations in oncogenic driver genes (P2, P5). P2, who developed MDS-EB 14 months after diagnosis, had two RUNX1 mutations at the time of progression. P5 had one RUNX1 and one EZH2 mutation, but without evidence of disease progression. Our results suggest that loss of monosomy 7 can occur in young patients with SAMD9L syndrome but is a rare event. If a watch and wait strategy is chosen, close monitoring with frequent bone marrow examinations including SAMD9L sequencing, cytogenetics and search for somatic oncogenic events is advised. Importantly, presence of severe infections, severe neutropenia, increase in blast percentage, and persistence of monosomy 7 beyond the age of 5 years should prompt timely allogeneic HSCT.

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk (“ugly”) locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT)

BackgroundThe presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients.MethodsThis multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life.DiscussionThis trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis.Trial registrationClinicaltrials.gov: NCT04838496, registered on 02–04-2021 Netherlands Trial Register: NL9790.Protocol versionVersion 3 dd 11–4-2022.

PROGNOSTIC FACTORS OF SQUAMOUS CELL CARCINOMA IN HARD PALATE, GINGIVA, AND UPPER ALVEOLAR RIDGE

<h3>Objectives</h3> Evaluate the sociodemographic profile, treatment, and prognostic factors of patients with oral squamous cell carcinomas of the hard palate, gingiva, and upper alveolar ridge (HPGUAR). <h3>Study Design</h3> This is a cohort study. Data were collected from patients of 2 head and neck surgery departments between 1999 and 2020. Clinicodemographic data, habits, site, size, clinical aspect, clinical staging, cervical metastasis, treatment, histologic features, margin status, and survival were collected. <h3>Results</h3> Forty-one patients were included. Among these, 61% were men with a mean age of 68.84 years (±13.9), smokers (46.3%), and nondrinkers (36.6%). The majority of cases were ulcers in the hard palate (51.2%), T4 (34.1%), N0 (63.4%), M0 (90.2%) in advanced clinical staging (51.2%). Surgery without adjuvant or neoadjuvant therapy was the most common treatment (48.8%). The "watch and wait strategy" for N0 tumors was adopted in 82.9% of cases. Four patients presented cervical metastases in follow-up (9.8%). Five patients died from the disease. The association between cervical metastasis and death was significant (<i>P</i> < .05). There was no association between cervical metastasis and other clinicodemographic variables. <h3>Conclusions</h3> Tumors in HPGUAR had a good response to surgical treatment and low index of cervical metastasis. Cervical metastasis was associated with death.

O034 Incidentally enlarged iliac lymph nodes in renal transplantation – a sting in the tail!

Abstract Introduction During renal transplant, lymphadenectomy around the iliac vessels is performed to provide adequate access. Enlarged iliac lymph nodes have unclear clinical significance and standard guidance. We audited lymph node histopathology to evaluate their significance. Methods Two audit cycles (January to August 2020 and September 2020 to October 2021, respectively) were performed. Following the first cycle, recommendation was that all enlarged lymph nodes should be biopsied. We reviewed patient histopathology and subsequent follow-up of patients with enlarged lymph nodes. Results 241 patients underwent renal transplantation, with 19 Patients having enlarged lymph nodes (median 35mm, range 12–77mm, figure 1) sent for histopathology. Specimens from 16 patients showed benign/reactive changes (7 patients CMV positive, 14 EBV positive). Two specimens contained no lymph node. One patient (CMV and EBV positive) demonstrated evidence of chronic lymphocytic leukaemia, followed up with a bone trephine biopsy and staging CT. Staging revealed lymphadenopathy on both sides of the diaphragm and an incidental 19mm renal cell carcinoma in the native right kidney. A watch and wait strategy was employed. All 19 patients who underwent lymph node sampling were alive at last follow up. Conclusion A literature review revealed no study into the best practice for managing incidentally enlarged lymph nodes. They are of unclear significance but may represent significant pathology requiring further follow up and management. We recommend that all lymph nodes with suspicious features and/or measuring &amp;gt;30mm are sampled for histopathology. Take-home message Enlarged lymph nodes (&amp;gt;30mm) should be biopsied, as they may be associated with significant pathology requiring follow up and/or intervention.

Primary Tumor Resection is Associated with Improved Disease-Specific Mortality in Patients with Stage IV Small Intestinal Neuroendocrine Tumors (NETs): A Comparison of Upfront Surgical Resection Versus a Watch and Wait Strategy in Two Specialist NET Centers.

Small intestinal neuroendocrine tumors (SI-NETs) often present with metastatic disease. An ongoing debate exists on whether to perform primary tumor resection (PTR) in patients with stage IV SI-NETs, without symptoms of the primary tumor and inoperable metastatic disease. The aim of this study was to compare a treatment strategy of upfront surgical resection versus a surveillance strategy of watch and wait. This was a retrospective cohort study of patients with stage IV SI-NETs at diagnosis, between 2000 and 2018, from two tertiary referral centers (Netherlands Cancer Institute [NKI] and Aintree University Hospital [AUH]) who had adopted contrasting treatment approaches: upfront surgical resection and watch and wait, respectively. Patients without symptoms related to the primary tumor were included. Multivariable intention-to-treat (ITT), per-protocol (PP), and instrumental variable (IV) analyses using 'institute' as an IV were performed to assess the influence of PTR on disease-specific mortality (DSM). A total of 557 patients were identified, with 145 patients remaining after exclusion of stage I-III disease or symptoms of the primary tumor (93 from the NKI and 52 from AUH). The cohorts differed in performance status (PS; p = 0.006) and tumor grade (p < 0.001). PTR was independently associated with reduced DSM irrespective of statistical methods employed: ITT hazard ratio [HR] 0.60, p = 0.005; PP HR 0.58, p < 0.001; and IV HR 0.07, p = 0.019. Other factors associated with DSM were age, PS, high chromogranin A, and somatostatin analog treatment. Taking advantage of contrasting institutional treatment strategies, this study identified PTR as an independent predictor of DSM. Future prospective studies should aim to validate these results.

PB2125: LYMPHOMATOID PAPULOSIS-LIKE (LYP-LIKE) AFTER BRENTUXIMAB VEDOTIN-CHP (BV-CHP) TREATMENT FOR ALK-NEGATIVE ANAPLASTIC LARGE CELL LYMPHOMA (ALCL)

Background: Lymphomatoid papulosis is an indolent form of CD30 primary cutaneous lymphoproliferative disorder characterized for recurrent crops of self-healing papular nodular lesions. Histological findings may overlap with those in primary cutaneous ALCL so clinical features and evolution determine the appropriate therapeutic approach. Most cases of LyP don’t require any treatment, but PUVA or low-dose oral methotrexate can reduce skin lesions. LyP-like is uncommon after a systemic ALCL. BV-CHP has become the new standard front-line treatment for ALCL in the last years; some aspects of the biological and clinical behavior of the disease with this new therapy are still under research. Aims: NA Methods: NA Results:Patient 1: 45 years female, diagnosed in January/20 with ALK-negative ALCL stage IV-A, IPI 3, involving multiple supra- and infradiaphragmatic lymphadenopathies, spleen, skin, bone and bone marrow. The diagnosis was performed by skin biopsy of an extensive ulcerated mass in the right chest area. FISH showed no rearrangements of DUSP22 and TP63. BV-CHP was started in January/20, achieving PR by PET-CT after 3 cycles. She completed 6 cycles. Four weeks after the last dose of chemotherapy she developed several papular skin lesions in the trunk and extremities. The skin biopsy was reported as ALCL. PET-CT showed metabolic CR at that time. After 3 weeks, the skin lesions spontaneously disappeared and she underwent ASCT conditioned with BEAM in July/20. Two months later, she developed new skin lesions and a new biopsy showed nonspecific findings: perivascular lymphocytic dermatitis with epidermal spongiotic changes. PET-CT showed two enlarged axillary lymphadenopathies with increased activity. A watch and wait strategy was adopted, until September/21 when she relapsed involving multiple lymphadenopathies, bone, spleen and new papulo-necrotic skin lesions. Skin biopsy showed a CD30+ lymphoprolipherative disorder. She received 3 cycles of ESHAP achieving PR, and an haploidentical stem cell transplantation was performed in January/22. Two months after transplant, the patient has no signs of disease and no skin lesions. Patient 2: 62 years male, diagnosed in August/21with systemic ALK-negative ALCL stage IV-B, IPI 3, with supra- and infradiaphragmatic lymphadenopathies and extensive colonic involvement. DUSP22-IRF4 and TP63 rearrangements were assessed, showing no abnormalities. Bone marrow and skin were not affected. He started front-line treatment with BV-CHP in September/21, with metabolic CR in the interim PET-CT after 4 cycles. He completed 6 cycles with good tolerance until late December/21. One month later, he developed papular and papulo-necrotic skin lesions in different evolutionary stages, affecting trunk, extremities and scalp. Skin biopsy was performed, showing a CD30+ lymphoprolipherative disorder. Another PET-CT demonstrated systemic CR. Clinicopathological findings were consistent with lymphomatoid papulosis. The patient underwent an ASCT as consolidation treatment. Currently, the skin lesions have involuted spontaneously. Image:Summary/Conclusion: These two similar cases illustrate an unusual scenario after systemic ALK-negative ALCL, both developed within weeks after frontline chemotherapy with BV-CHP. Diagnosis and therapeutic decisions are challenging. Further experience with this new regimen will reveal whether the addition of BV may play a role in the development of this condition, and whether the clinical course is the same as primary cases of LyP or precedes a relapse of systemic lymphoma.

Role of Local Excision for Suspected Regrowth in a Watch and Wait Strategy for Rectal Cancer.

Simple SummaryRectal cancer patients with a clinical complete response to neoadjuvant treatment are eligible for Watch and Wait as an alternative to total mesorectal excision. However, in patients with local regrowth, major surgery is still the standard of care. The present study evaluates the role of local excision for suspected local regrowth in a large Watch and Wait cohort, in terms of long-term outcomes. This study shows excellent overall survival and a good organ preservation rate. Patients who developed locoregional recurrence after initial local excision for regrowth were all successfully treated with salvage surgery. This study shows that local excision can provide maintenance of organ preservation without an obvious compromise in surgical or oncological safety. Local excision for suspected regrowth in patients following Watch and Wait can be a safe alternative for total mesorectal excision in selected patients with a strong wish to preserve their rectum.Rectal cancer patients with a clinical complete response to neoadjuvant (chemo)radiation are eligible for Watch and Wait (W&W). For local regrowth, total mesorectal excision (TME) is considered the standard of care. This study evaluated local excision (LE) for suspected local regrowth. From 591 patients prospectively entered into a national W&W registry, 77 patients with LE for regrowth were included. Outcomes analyzed included histopathologic findings, locoregional recurrence, long-term organ preservation, and colostomy-free and overall survival. In total, 27/77 patients underwent early LE (<6 months after neoadjuvant radiotherapy) and 50/77 underwent late LE (≥6 months). Median follow-up was 53 (39–69) months. In 28/77 patients the LE specimen was histopathologically classified as ypT0 (including 9 adenomas); 11/77 were ypT1, and 38/77 were ypT2–3. After LE, 13/77 patients with ypT2–3 and/or irradical resection underwent completion TME. Subsequently, 14/64 patients without completion TME developed locoregional recurrence, and were successfully treated with salvage TME. Another 8/77 patients developed distant metastases. At 5 years, overall organ preservation was 63%, colostomy-free survival was 68%, and overall survival was 96%. There were no differences in outcomes between early or late LE. In W&W for rectal cancer, LE can be considered as an alternative to TME for suspected regrowth in selected patients who wish to preserve their rectum or avoid colostomy in distal rectal cancer.

Predicting pathologic complete response in locally advanced rectal cancer patients after neoadjuvant therapy: a machine learning model using XGBoost

PurposeWatch and wait strategy is a safe and effective alternative to surgery in patients with locally advanced rectal cancer (LARC) who have achieved pathological complete response (pCR) after neoadjuvant therapy (NAT); present restaging methods do not meet clinical needs. This study aimed to construct a machine learning (ML) model to predict pCR preoperatively.MethodsLARC patients who received NAT were included to generate an extreme gradient boosting-based ML model to predict pCR. The group was divided into a training set and a tuning set at a 7:3 ratio. The SHapley Additive exPlanations value was used to quantify feature importance. The ML model was compared with a nomogram model developed using independent risk factors identified by conventional multivariate logistic regression analysis.ResultsCompared with the nomogram model, our ML model improved the area under the receiver operating characteristics from 0.72 to 0.95, sensitivity from 43 to 82.2%, and specificity from 87.1 to 91.6% in the training set, the same trend applied to the tuning set. Neoadjuvant radiotherapy, preoperative carbohydrate antigen 125 (CA125), CA199, carcinoembryonic antigen level, and depth of tumor invasion were significant in predicting pCR in both models.ConclusionOur ML model is a potential alternative to the existing assessment tools to conduct triage treatment for patients and provides reference for clinicians in tailoring individual treatment: the watch and wait strategy is used to avoid surgical trauma in pCR patients, and non-pCR patients receive surgical treatment to avoid missing the optimal operation time window.

Circulating cell-free DNA as predictor of pathological complete response in locally advanced rectal cancer patients undergoing preoperative chemoradiotherapy

BackgroundThe watch and wait (W&W) strategy is proposed for patients with locally advanced rectal cancer (LARC) achieving clinical complete response (cCR) after neoadjuvant radiotherapy. cCR is only in partial concordance with pathological complete response (pCR) due to persisting viable tumour cells. The aim was to investigate circulating-free-deoxyribonucleic-acid (cfDNA) as a biomarker for prediction of pCR. Materials and methodsPatients treated with neoadjuvant radiotherapy for LARC, were included in a prospective biomarker study in Aarhus, Denmark from 2017 to 2020. Plasma cfDNA levels were analysed by a direct fluorescent assay (DFA). Surgical specimens were reviewed by pathologists to categorize response to cytotoxic therapy. ResultsIn total, 76 patients were included with plasma available at baseline (n = 70), mid therapy (n = 50), and end of therapy (n = 54). Higher cfDNA levels were observed in LARC patients compared with healthy subjects (p < 0.01). By ROC analysis (AUC: 0.87 (95% CI, 0.81–0.92)) the optimal cut-off was 0.71 ng/µL for differentiation between healthy subjects and LARC patients. Thirteen patients obtained pCR with a median cfDNA level of 0.57 ng/µL at end of therapy. Patients with cfDNA levels at end of therapy below the cut-off (p < 0.02) and ‘cfDNA responders’ with descending levels greater than the 75th percentile during therapy had a significantly higher chance of pCR (p < 0.01). ConclusionThis hypothesis generating study indicates that low cfDNA levels at end of treatment or ́cfDNA responderś might be associated with pCR. Quantification of cfDNA by the rapid and feasible DFA analysis could potentially facilitate personalized follow-up as a complementary tool to identify candidates for a W&W strategy.

Protective ileostomy increased the incidence of rectal stenosis after anterior resection for rectal cancer

BackgroundIn most of the views, rectal stenosis after anterior resection for rectal cancer results from pelvic radiotherapy. However, patients without receiving radiotherapy also suffer stenosis. In this study, we evaluated the factors associated with rectal stenosis after anterior rectal resection (ARR).MethodsWe conducted a retrospective study with ARR patients who underwent neoadjuvant chemoradiotherapy and the patients without radiotherapy. Patients who received watch and wait strategy with a clinical complete response after chemoradiotherapy were also included. Patients with colonoscopy follow-up were included for further analyses; 439 patients who underwent neoadjuvant chemoradiotherapy; 545 patients who received ARR without radiotherapy and 33 patients who received watch and wait strategy. Stenosis was diagnosed when a 12-mm diameter colonoscopy could not be passed through the rectum. Univariate and multivariate logistic regression analyses were performed to identify variables associated with rectal stenosis.ResultsAccording to the multivariate analysis in patients receiving ARR, both protective stoma and preoperative radiotherapy affected the occurrence of stenosis, with the odds ratios (ORs) of 3.375 and 2.251, respectively. According to the multivariate analysis, a preventive ileostomy was the only factor associated with stenosis both in patients receiving preoperative radiotherapy and without radiotherapy. Non-reversal ileostomy and long time between ileostomy and restoration increased the possibility of stenosis. In 33 patients who received watch and wait strategy, only one patient (3%) experienced stenosis.ConclusionBoth surgery and radiotherapy are risk factors for rectal stenosis in rectal cancer patients. Compared to preoperative radiotherapy, a protective ileostomy is a more critical factor associated with rectal stenosis.

Does Pathological Complete Response after Neoadjuvant Therapy Influence Postoperative Morbidity in Rectal Cancer after Transanal Total Mesorectal Excision?

It is still unclear if pathological complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) in patients treated for rectal cancer causes worse postoperative outcomes, especially after transanal total mesorectal excision (TaTME). Worse postoperative outcomes might be an argument for an organ preserving watch and wait strategy in fragile patients and patients with comorbidities. The aim of this study is to evaluate whether patients treated for rectal cancer who had pCR to neoadjuvant therapy develop worse postoperative outcomes after TaTME than patients without complete response. Comparative retrospective analysis (with nearest neighbor matching algorithm) of postoperative outcomes in two groups of patients, with pCR, n = 15 and without pCR (non-pCR), n = 57. All patients were operated on only by one surgical approach, TaTME, for middle and distal rectal tumors. All procedures were performed by one surgical team between 2014 and 2020 at the University Hospital Brno in Czech Republic. Overall morbidity was comparable between the groups (pCR group - 53.8% vs. non-pCR - 38.6%, p = 0.381). Anastomotic leak (AL) was observed in 33.3% of patients with pCR and in 17.5% of patients in the non-pCR group without statistical significance (p = 0.281). In conclusion, pathological complete response after neoadjuvant therapy does not appear to affect postoperative morbidity in rectal cancer after TaTME. Therefore, in patients with complete response who are not adherent to W&W surveillance, surgical resection can be perform without increased postoperative complications.

Endoscopy-Based Deep Convolutional Neural Network Predicts Response to Neoadjuvant Treatment for Locally Advanced Rectal Cancer.

Background and Aims: Although the wait and watch (W&W) strategy is a treatment choice for locally advanced rectal cancer (LARC) patients who achieve clinical complete response (cCR) after neoadjuvant therapy (NT), the issue on consistency between cCR and pathological CR (pCR) remains unsettled. Herein, we aimed to develop a deep convolutional neural network (DCNN) model using endoscopic images of LARC patients after NT to distinguish tumor regression grade (TRG) 0 from non-TRG0, thus providing strength in identifying surgery candidates. Methods: A total of 1000 LARC patients (6,939 endoscopic images) who underwent radical surgery after NT from April 2013 to April 2021 at the Sixth Affiliated Hospital, Sun Yat-sen University were retrospectively included in our study. Patients were divided into three cohorts in chronological order: the training set for constructing the model, the validation set, and the independent test set for validating its predictive capability. Besides, we compared the model’s performance with that of three endoscopists on a class-balanced, randomly selected subset of 20 patients’ LARC images (10 TRG0 patients with 70 images and 10 non-TRG0 patients with 72 images). The measures used to evaluate the efficacy for identifying TRG0 included overall accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUROC). Results: There were 219 (21.9%) cases of TRG0 in the included patients. The constructed DCNN model in the training set obtained an excellent performance with good accuracy of 94.21%, specificity of 94.39%, NPV of 98.11%, and AUROC of 0.94. The validation set showed accuracy, specificity, NPV, and AUROC of 92.13%, 93.04%, 96.69%, and 0.95, respectively; the corresponding values in the independent set were 87.14%, 92.98%, 91.37%, and 0.77, respectively. In the reader study, the model outperformed the three experienced endoscopists with an AUROC of 0.85. Conclusions: The proposed DCNN model achieved high specificity and NPV in detecting TRG0 LARC tumors after NT, with a better performance than experienced endoscopists. As a supplement to radiological images, this model may serve as a useful tool for identifying surgery candidates in LARC patients after NT.

Short-term and long-term treatment outcomes in patients with lower and middle rectal cancer with complete clinical and pathomorphological response after comprehensive treatment

Objective: to compare short-term and long-term treatment outcomes between patients with lower and middle rectal cancer with complete clinical and pathomorphological response after comprehensive treatment.Materials and methods. we performed retrospective analysis of treatment outcomes in patients with lower and middle rectal cancer. The experimental group included 27 patients with complete clinical response, whereas the control group comprised 31 patients with complete pathomorphological response (ypT0n0m0) who had undergone total mesorectal excision following neoadjuvant therapy. The main evaluated parameters included postoperative complications, proportion of R0 resections, proportion of sphincter-preserving surgeries, 2-year overall survival, and progression-free survival.Results. At a median follow-up time of 41 months (range: 25–114 months), 2 patients from the experimental group had progressive disease registered 18 and 19 months after treatment initiation; both patients underwent abdominoperineal extirpation of the rectum. The remaining 25 patients had sphincter sparing surgeries. At a median follow-up time of 48 months (range: 24–101 months), one patient was found to have liver metastasis 5 months following treatment initiation. He underwent simultaneous surgery that included low anterior resection of the rectum and liver resection and had no postoperative complications. In the group of surgical treatment, all patients underwent radical surgeries (R0), including those with permanent stoma formation (n = 11; 35.5 %) or preventive stoma formation (n = 20; 64.5 %) with subsequent bowel repair. The 2-year overall survival rate was 100 % in both groups. The 2-year progression-free survival rate was 92.6 % in the experimental group and 96.8 % in the control group (p = 0.473).Conclusion. The watch and wait strategy with active dynamic follow-up is a safe alternative to surgery in patients with complete clinical response after neoadjuvant therapy, since it ensures the results equivalent to those in patients with complete pathomorphological response.

Place of radiotherapy in the treatment of rectal cancer in the elderly

Rectal cancer is a common disease of the elderly. Current treatment recommendations are established for young subjects in good general health condition, without taking into account the frailty, comorbidities and polymedications inherent in patients over 75 years old. For locally advanced lower and middle rectal cancers (T3, T4 or N+), these are based on variations of regimens including neoadjuvant chemoradiotherapy, surgery of the rectum with total removal of the mesorectum, and a possibility of adjuvant chemotherapy. This restrictive treatment presents a problem of compliance and is not without adverse effects. Treatment by short exclusive radiotherapy or chemoradiotherapy with close monitoring according to the Watch and Wait strategy can be proposed to fragile patients not eligible for surgery, even if there is a non-negligible risk of recurrence.

Watch and Wait Strategy for Rectal Cancer: How Long Should We Wait for a Clinical Complete Response?

The objective of this study was to determine how long to wait in locally advanced rectal tumor (LARC) patients who receive total neoadjuvant therapy (TNT) and achieve a clinical complete response (cCR), and to identify the clinical parameters that affect the waiting period for the watch-and-wait strategy (W &W). The data of patients who achieved cCR between February 2015 and June 2020 were examined retrospectively. The week in which patients with cCR at the end of TNT achieved clearance was determined by reanalyzing recorded endoscopy video images. In the assessment at the time of the initial diagnosis, tumor characteristics, such as digital rectal examination findings, MRI stage, location with respect to the puborectalis muscle, annularity, and tumor size, were recorded prospectively. A total of 54 patients were included in this study. According to the MRI-T stage, 14 cases were cT3a, 22 were cT3b, and 18 were cT3c-T4. Forty-four percent of the cases achieved cCR at 8-10 weeks, 19% at 12-16 weeks, 20% at 16-22 weeks, and 17% at 20-26 weeks. Patients with tumors that were early MRI-T stage (cT3a), negative clinical circumferential resection margin, mobile, small (≤4 cm), located above the puborectalis muscle and showed <180 degrees annularity achieved cCR significantly earlier than those with other tumors (p<0.05). In this study, cCR was achieved in less than half (44%) of the cases during the 8-10 week waiting period. In the W&W strategy, the initial assessment for cCR seems insufficient, and we may need to wait up to 26-30 weeks, especially in patients with advanced-stage tumors.

Clinical features and outcomes of duodenal-type follicular lymphoma: A single-center retrospective study.

Duodenal‐type follicular lymphoma (FL) is a rare and newly recognized disease. Few data are available on the outcomes and treatment strategies for patients with duodenal‐type FL. We aimed to investigate the clinical features and outcomes of duodenal‐type FL. We defined duodenal‐type FL as involvement of the duodenum, without nodal or extranodal lesions other than intestinal lesions, pathologically diagnosed as FL. We reviewed 26 patients with duodenal‐type FL between January 2011 and December 2020 at Kobe City Hospital Organization, Kobe City Medical Center General Hospital. In particular, patients were selected for the watch and wait (WW) strategy and followed up with regular esophagogastroduodenoscopy about once a year at our institution. The patient characteristics were as follows: median age 63.5 years (range: 42–78), sex (male, 15; female, 11), stage (I, 26), and grade (I, 26). Regarding treatment strategies, 23 patients were selected for the WW strategy, and three patients received initial rituximab therapy. The median follow‐up period was 65.5 months (range: 0.2–109). Five‐year progression‐free survival and 5‐year overall survival rates were 86.3% and 100%, respectively. Among the 23 patients selected for the WW strategy, six had spontaneous complete regression, and 14 had stable disease, and three had progressive disease, including one with histologic transformation. The WW strategy for patients with duodenal‐type FL could be an appropriate and safe treatment option. However, in several cases, disease progression was documented, and regular follow‐up is important.