Watch Approach Research Articles

Watch and wait approach in rectal cancer: Current controversies and future directions.

According to the main international clinical guidelines, the recommended treatment for locally-advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. However, doubts have been raised about the appropriate definition of clinical complete response (cCR) after neoadjuvant therapy and the role of surgery in patients who achieve a cCR. Surgical resection is associated with significant morbidity and decreased quality of life (QoL), which is especially relevant given the favourable prognosis in this patient subset. Accordingly, there has been a growing interest in alternative approaches with less morbidity, including the organ-preserving watch and wait strategy, in which surgery is omitted in patients who have achieved a cCR. These patients are managed with a specific follow-up protocol to ensure adequate cancer control, including the early identification of recurrent disease. However, there are several open questions about this strategy, including patient selection, the clinical and radiological criteria to accurately determine cCR, the duration of neoadjuvant treatment, the role of dose intensification (chemotherapy and/or radiotherapy), optimal follow-up protocols, and the future perspectives of this approach. In the present review, we summarize the available evidence on the watch and wait strategy in this clinical scenario, including ongoing clinical trials, QoL in these patients, and the controversies surrounding this treatment approach.

Chemoradiotherapy alone or chemoradiotherapy followed by surgery in rectal cancer

In locally advanced rectal cancer, neoadjuvant chemoradiotherapy provides a significant benefit to local cancer control in addition to total mesorectal excision. However, in 10–40% of all patients, a complete clinical remission can be detected after completion of chemoradiotherapy. Recent studies have shown that those patients omitting radical surgery after successful neoadjuvant pretreatment can be safely managed within a close follow-up network without compromising short-term overall and disease-free survival. However, available data suggest that 20–30% of all patients assigned to a watch and wait regimen will eventually have to be transferred to surgical management due to local recurrence. Careful patient selection is key for a successful watch and wait approach and the choice of non-operative management should not be made after completion of staging but rather after neoadjuvant chemoradiotherapy. Selected patients need to be thoroughly informed that there is still no standardized follow-up protocol and no predefined follow-up period.

Leukemic Non-nodal Mantle Cell Lymphoma: Diagnosis and Treatment.

Mantle cell lymphoma (MCL) encompasses nearly 6% of all the non-Hodgkin lymphomas. It is considered an incurable neoplastic process arising from B cells. The cytogenetic abnormality t(11;14) (q13; q32) leading to cyclin D1 overexpression is the sentinel genetic event and provides an exceptional marker for diagnosis. MCL is generally considered to have an aggressive course as compared with other indolent lymphomas with traditionally reported median survival of 3-5years. According to the 2016 WHO classification, there are two major known variants of MCL: classical which affects the lymph nodes and extra nodal sites and leukemic non-nodal MCL (L-NN-MCL) which characteristically involves the bone marrow, peripheral blood, and the spleen. It is important to distinguish between classical and leukemic non-nodal MCL since the latter variant of MCL follows a rather indolent course with a wait and watch approach in order to avoid overtreatment. However, a subset of patients with L-NN-MCL can transform into a more aggressive course requiring treatment. Current evidence suggests those patients with alteration in TP53 gene do not respond to standard chemotherapy agents and may need targeted therapy. In this review, we describe the characteristics of L-NN-MCL, its diagnosis, and management.

Splenic Marginal Zone Lymphoma: A U.S Population-Based Survival Analysis (1997-2016)

INTRODUCTION: Splenic marginal zone lymphoma (SMZL) is a rare and indolent form of NHL with no standard treatment due to scarcity of clinical trials. Watch and wait approach, single agent rituximab or with chemotherapy and splenectomy are valid treatment approaches. No population-based studies examining the impact of chemotherapy and splenectomy on survival of SMZL patients are available. Thus, we decided to compare survival outcomes by clinical factors in SMZL patients deposited in the SEER database, emphasizing in the role of splenectomy on survival outcomes. METHODS: Retrospective analysis of SMZL cases in the SEER database from 1997 to 2016.SEER collects cancer incidence and survival data from population-based cancer registries covering 34% of the U.S. population. PATIENTS: SEER database was queried for SMZL patients at all ages from 1997 to 2016. Cases without histologic confirmation or no survival data were excluded. Demographic and clinical variables (age, sex, race, ethnicity, B-symptoms, Ann-Arbor stage, DLBCL transformation, first malignancy, chemotherapy with or without rituximab, splenectomy and radiotherapy) were summarized by descriptive statistics. Logistic regression used to determine variables associated with splenectomy. Overall survival (OS) and Cancer-specific survival (CSS) were the major end-points, estimated by Kaplan-Meier method. Cox regression used to calculate Hazard Ratios. RESULTS: 2212 patients met inclusion criteria, with a median age of 68yo (25-96). Patient characteristics were a follows: males (n=1152, 52.1%); whites (n=1991, 90.0%), blacks (112, 5.1%); Non-Hispanics (n=2049, 92.6%); B-symptoms (n=461, 20.8%); first malignancy (n=1754, 79.3%); Ann-Arbor Stage I (429, 19.4%), Stage IV (n=1351, 61.1%); DLBCL transformation (n=84, 3.8%). Adjusted Odds ratio (aOR) were used to compare splenectomy versus non-splenectomy treated patients: ≥60yo (aOR 0.49;0.40-0.62), males (aOR 0.77;0.64-0.93). Median survival of all the patients was 120 months (95%CI:111-132); On univariate analysis: shorter OS was significantly associated with age ≥60(HR 3.55;2.87-4.38) and non-first malignancy(HR 1.6;1.36-1.88), while shorter CSS was significantly associated with age ≥60(HR 1.76;1.33-2.34), B-symptoms (HR 1.93;1.44-2.60), Stage IV (HR 1.62;1.15-2.28), DLBCL transformation (HR 2.27;1.55-3.33) and treatment with chemotherapy (HR 1.54;1.22-1.94). On multivariate analysis, shorter OS was significantly associated with age ≥60(HR 3.52;2.83-4.37), male sex (HR 1.15;1.00-1.33), B-symptoms (HR 1.23;1.01-1.51) and non-first malignancy (HR 1.42;1.20-1.67). Shorter CSS was significantly associated with age ≥60(HR 2.15;1.61-2.87), Hispanic ethnicity (HR 1.44;1.00-2.07), B-symptoms (HR 1.77;1.30-2.39), DLBCL transformation (HR 2.03;1.38-2.99) and treatment with chemotherapy (HR 1.38;1.07-1.77). Ann Arbor staging and splenectomy were not associated with OS or CSS. CONCLUSIONS: Older age, Hispanic ethnicity, B-symptoms, DLBCL transformation, and treatment with chemotherapy were associated with poor lymphoma-specific survival. Although, age<60 and female gender were associated higher odds to undergo splenectomy, splenectomy had no impact on the risk of lymphoma-related death or OS. This retrospective study demonstrates that chemotherapy treatment (excluding rituximab) was associated with inferior outcomes in SMZL, while advanced Ann-Arbor stage was not associated with shorter survival as is observed in other indolent lymphomas that commonly present at advanced stage. Table Disclosures Alderuccio: Targeted Oncology: Honoraria; Foundation Medicine: Other: Immediate family member; Agios: Other: Immediate family member; Puma Biotechnology: Other: Immediate family member; OncLive: Consultancy; Inovio Pharmaceuticals: Other: Immediate family member. Lossos:NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Janssen Scientific: Membership on an entity's Board of Directors or advisory committees.

World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management.

The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 109 /L, and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ-hybridization, flow immunophenotyping, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm. Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes. This includes the major category "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2", and the MPN subtype, "chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS). Lymphocyte-variant hypereosinophilia is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion. The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (eg, <1.5 × 109 /L) without symptoms or signs of organ involvement, a watch and wait approach with close-follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES. Hydroxyurea and interferon-alfa have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. The use of antibodies against interleukin-5 (IL-5) (mepolizumab), the IL-5 receptor (benralizumab), as well as other targets on eosinophils remains an active area of investigation.

Prostate Cancer in an Incarcerated Population: Patient Characteristics and Treatment

Incarcerated inmates within the Federal Correctional system who are newly diagnosed with cancer are generally transferred to the Cancer Center within the Federal Medical Center Hospital (FMC) in Butner , North Carolina. At the FMC, full time, in house, board certified oncologists offer treatment consistent with the community standard of care. This study looked at the characteristics and oncologic treatment of men transferred to FMC due to the diagnosis of prostate cancer. This was a retrospective chart review. All men with histologically confirmed and newly diagnosed prostate cancer admitted to the FMC during the period of Jan 1 , 2018-Jan 1, 2019 were analyzed. Patients were transferred from within the continental United States and Hawaii. A total of 82 men were transferred: Age range: (36-78 years, mean 59 yrs) with 30% white, 50% African American, and 20% Hispanic. Diagnosis was most commonly due to LUTs syndrome, noted in 85% of men. Two men were diagnosed based on development of symptomatic bone mets. PSA levels for non-metastatic prostate ca at diagnosis ranged from (3-158 , mean 14.1 ng/ml). Gleason score of 9 (n=7), 8 (n=9), 7 (n=37) or 6 (n=27) were noted. A total of 89% of curative patients had high grade/high volume disease and/or PSA greater than 10 ng/ml. Biopsy was by an ultrasound guided trans- rectal approach. Bone scan and pelvic CT were routinely obtained in all patients with Gleason 7 disease or higher. Genomic testing was rarely done. A total of 5 patients requested a watch and wait approach, 3 had surgery, and the remainder underwent external beam radiation therapy. XRT was delivered by an IMRT approach in all cases, with all patients achieving 75.6 Gy in 42 equivalent fractions. Lupron was prescribed in 71 curative cases for 6 or 18 months depending on stage of disease. Federal Inmates diagnosed with prostate cancer appear to have higher Gleason Scores , PSA levels, and volumes of disease then what may be currently expected in the general population. As no prostate screening system is in place ,these more advanced malignancies likely represent the natural history of an unscreened population, which also appears to be the trend in the general population. All incarcerated patients in this study have been treated as per national guidelines. Radiation Therapy is the treatment most commonly taken, generally in combination with androgen blockade due to the higher PSA, grade and advanced disease noted.

Watch and Wait Approach for Re-excision After Unplanned Yet Macroscopically Complete Excision of Extremity and Superficial Truncal Soft Tissue Sarcoma is Safe and Does Not Affect Metastatic Risk or Amputation Rate.

The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown. The aim of this study was to evaluate the impact of delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation. Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C). Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (p = 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (p = 0.938); RE (p = 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (p = 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (p = 0.41). Factors influencing LRFS were adjuvant radiotherapy [hazard ratio (HR) 0.21; p = 0.0001], initial R0 resection (HR 0.24, p = 0.0001), and Group A (HR 0.44; p = 0.01). Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.

PB1913 CIRS SCORE AS A RELIABLE COMORBIDITY EVALUATION TOOL MAY INFLUENCE THERAPEUTIC DECISIONS IN ELDERLY CLL PATIENTS

Background:Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the elderly population and many of these patients have multiple comorbidities, which might limit the eligibility for upfront chemoimmunotherapy options. The Cumulative Illness Rating Scale (CIRS) score seems to be a reliable tool for assessment of the burden of comorbidity in elderly cancer patients. It may identify fit and unfit CLL patients and influence the therapeutic decision‐making process.Aims:The primary objective of our study was to assess the CIRS score status in CLL patients in real clinical practice. The secondary objective was to analyze which treatment option was used in each patient's group, classified according to CIRS.Methods:In our prospective, single‐center study we focused on CLL patients that visited the University clinic for hematology in Skopje between March 20th 2017 and January 22nd 2019. Comorbidity was assessed by the CIRS‐G score in all patients included in our study (n = 56) prior to reaching a multidisciplinary treatment decision.Results:In our series, 56 CLL patients; 30 (53.6%) males and 26 (46.4%) females, were included. Median age was 69 (± 9.4) years (range 38‐85). Comorbidities were identified in 80.4% of the study population, with an average CIRS score of 3.9 (range 0‐13). Only 19.6% of the patients were comorbidity free. There was a positive correlation between the CIRS score and the age (rs = 0.2276, p = 0.04). Two thirds, or 67.9% of the patients had a CIRS score &lt;6, 21.4% had CIRS score between 6 and12 and CIRS score was &gt;12 in only 8.9% of patients. The three most common comorbidities were related to affections of the vascular system (41.1%), endocrine‐metabolic disorders (32.1%), and respiratory system disorders (17.9%). Only 16.1% of the patients had only 1 affected organ or system, other than hematological issues, while 64% of the patients had ≥2 affected systems. In 33.9% of the study patient cohort, the watch and wait approach was the standard of care; 66.1% of patients were eligible for treatment as follows: chemotherapy (chlorambucil, fludarabine + cyclophosphamide, bendamustine) only (30.4%), rituximab‐based therapy (33.9%) and 1.8% of patients, due to the high comorbidity burden, received only supportive care. There was a stable trend of correspondence between the CIRS score assessment and the treatment option prescribed (rs = 0.7188, p &lt; 0.000001). Despite their eligibility for novel therapies (e.g. obinutuzumab, ibrutinib, idelalisib etc.) none of the patients received them due to their local unavailability.Summary/Conclusion:Our study shows that comorbidity is a very common feature in CLL patients and that it is increasing with age. Despite the fact that 8 out of 10 patients had at least one affected organ/system, the general comorbidity burden was low. CIRS is helpful in identifying the best treatment combination for the patients, that will enhance achieving long‐term control of CLL, maintaining an optimal quality of life level.

Patient reported outcome measures (PROMs) in patients (pts) with locally advanced rectal cancer (LARC) managed with a watch and wait (W&amp;W) approach after a clinical complete response to chemoradiotherapy (CRT).

e15173 Background: PROMs have not been adequately studied in LARC pts who are managed with W&amp;W after a clinical complete response to CRT. The objectives of this study were to evaluate: quality of life measures, bowel function, Fear of Cancer Recurrence (FCR) and survivors’ needs, in this population. Methods: Data were collected from the Flinders Medical Centre W&amp;W prospective database. Questionnaires including Self-Administered Comorbidity (SCQ), EORTC QLQ-C30 and -CR29, EQ-5D-5L, MSKCC Bowel Function Instrument (MBFI), Low Anterior Resection Syndrome (LARS) score, Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF), Cancer Survivors’ Unmet Needs (CaSUN) and Response Efficacy Score (RES) were sent via mail to eligible pts according to a Tailored Design Method. Descriptive statistical analyses were conducted. Results: Of 40 eligible pts, 21 (52.5%) responded: 15 (71%) were male, median age at diagnosis was 66 years (34-81). 5 developed local re-growth (1 had local excision and 4 had ultra-low anterior resection). Median time from end of CRT to data collection was 39.8 months (6.0-77.5). The mean SCQ score was 5.7 (SD 5.5). Mean EQ-5D-5L utility score was 0.84 (SD 0.13), mean EQ-VAS score was 81.9 (SD 12.7) and mean EORTC QLQ global health status score was 76.2 (SD 19.2). The most common symptoms were fatigue (90%), pain (67%) and flatulence (67%). In pts without a re-growth (n = 16), the mean MBFI total score was 27.9 (SD 7.7); based on LARS score: 6 (38%) had no LARS, 5 (31%) had minor LARS and 5 (31%) had major LARS. Mean FCRI-SF score was 11.8 (SD 6.1), clinical level FCR was reported by 2 (9.5%) [cut-off 22] and 4 (19%) pts [cut-off 16]. 10 (47%) reported unmet needs: the most common area was Comprehensive Cancer Care n = 9 (42%). On RES, of 20 responders, 19 (95%) believed W&amp;W was a worthwhile and effective strategy. Conclusions: The most commonly reported symptoms included fatigue, pain and flatulence. LARS was common: in the absence of surgery, LARS is due to CRT. Clinical FCR was uncommon. The majority believed W&amp;W was worthwhile and effective. Larger comparative studies are needed in this group of pts.

Short course radiation therapy for rectal cancer in the elderly: can radical surgery be avoided?

Rectal cancer in elderly patients can be difficult to manage. Short course radiation therapy (SCRT) has shown to be effective when given immediately prior to surgery. Here we report outcomes of elderly patients who underwent SCRT either alone or prior to resection. Between 2010 and 2015, elderly patients with rectal cancer and no distant metastatic disease were identified. Symptoms at diagnosis, therapies, toxicities, and pathologic and clinical response were recorded from patient charts. The SCRT prescription dose was 5 Gy ×5 to the rectal tumor and 4 Gy ×5 to the mesorectum, omitting the iliac nodes. Twenty patients were identified with median age of 85 years (range, 71-93 years). No patient received systemic therapy. Sixty percent of patients were cT3 at diagnosis. Half underwent resection post SCRT and half received SCRT as definitive therapy. The 1- and 2-year overall survival was 75% and 54%. Overall survival did not differ between patients treated with SCRT and surgery compared to SCRT alone (P=0.8). Of the 10 surgical patients, 3 had a complete pathologic response at time of resection and 3 patients died within 2 weeks due to perioperative complications. Of patients treated with SCRT alone, 8 were symptomatic at presentation and 5 had a clinician defined symptomatic response. No patient treated with SCRT monotherapy required additional palliative measures for outflow obstruction, but 2 progressed locally and died. SCRT is well tolerated, results in pathologic complete responses in a small percentage of patients, and achieves 63% symptom improvement rate as monotherapy. A high peri-operative complication rate was observed in this small series. In elderly patients, SCRT as initial treatment with a watch and wait approach for surgery is feasible and should be evaluated prospectively.

Watch and wait approach following neoadjuvant chemoradiotherapy for rectal cancer patients: A single-centre experience.

681 Background: A watch-and-wait approach for patients with clinical complete response to neoadjuvant chemoradiation could avoid the morbidity of conventional surgery for rectal cancer. Here, we report the survival outcome of patients with this strategy in our center. Methods: We retrospectively analyzed the rectal cancer patients who received neoadjuvant chemoradiotherapy since 2015 in our center. Preoperative regimen included long-course radiotherapy (50 Gy / 25 Fx) combined fluoropyrimidin–based chemotherapy concurrently. MRI and endoscopic evaluation were performed after preoperative treatment. Patients with complete tumor response were referred to the “watch-and-wait” approach and omitted the surgery. Four to six cycles of consolidation chemotherapy were performed. Patients were followed up clinically, endoscopically, and radiologically to assess for local recurrence or disease progression. Results: From January 2015 to March 2018, a total of 47 patients with rectal cancer in our center received conservative treatment following neoadjuvant therapy. The median age of the patients is 58 (53-66). The proportions of stages I to IV are 4.3%, 12.8%, 70.2%, 8.5%, respectively. After a median follow-up of 20 month, tumor regrowth occurred in five out of 47 (10.6%) patients. All local regrowth was diagnosed in the first two years, and four out of five (80%) of local regrowth was located in the bowel wall. All patients underwent salvage surgery. Distant metastasis was diagnosed in four of 47 patients (8.5%). two-year overall survival was 89.9%, and two-year disease-free survival was 76.5%. Conclusions: Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve a complete response to individualized neoadjuvant CRT. The survival of patients is not impaired with “watch-and-wait” strategy.

Feasibility of Wait and Watch Approach after Neoadjuvant Chemoradiotherapy in Rectal Cancer in Low- and Middle-Income Countries: Initial Experience in Tertiary Cancer Centre in India

Wait and watch (W & W) approach after response to neoadjuvant chemoradiotherapy (NACRT) in locally advanced rectal cancer (LARC) is standard of care in medically inoperable patients. Otherwise, its use is recommended in a controlled research setting. In low- and middle-income countries (LMICs) there is presumed noncompliance with strict follow-up protocol of W & W approach due to geographical vastness, limited resources, and poor socioeconomic status. The objective of this study is to assess the feasibility, acceptance, and subsequent compliance to W & W approach after the clinical complete response (cCR) and near clinical complete response (ncCR) to NACRT in LARC. Patients diagnosed with LARC from September 2013 to January 2018 who had cCR and ncCR to NACRT (Radiotherapy dose 45-55 Gy) were offered either surgery as standard of care or W & W approach with strict follow up protocol consisting of regular digital rectal examination (DRE), magnetic resonance imaging (MRI) and sigmoidoscopy with informed consent. The cCR was defined as no palpable abnormality on DRE, white scar with telangiectasia on sigmoidoscopy and absence of residual tumor on T2W-MRI. The ncCR was defined as superficial soft irregularity or small flat ulcer at DRE, small residual flat ulcer or irregular wall thickening on the sigmoidoscopy and significant downstaging with/without residual fibrosis, but with a heterogeneous or irregular aspect on MRI. The first evaluation was done at 6-8 weeks after completion of NACRT and subsequently at 12 weeks. In this retrospective observational study, data was extracted from prospectively maintained rectal cancer database at our institution. All 28 patients (stage II = 14%, stage III = 86%) with cCR and ncCR preferentially opted for W & W approach over surgery. All 28 patients complied to a strict follow-up protocol of W & W approach. Median follow up was 47 weeks (Range 8 – 397 weeks). Eleven patients had cCR and 17 patients had ncCR after NACRT. All the 11 patients with cCR had no local regrowth, no regional or distant metastasis, or death. Five patients out of the total 17 patients in ncCR group developed cCR up to 1 year, 9 patients maintained ncCR, 1 patient developed regional and distant metastasis and died. Two patients underwent surgery due to the persistent ulcer at 21 weeks and 27 weeks after NACRT. Abdominoperineal resection was done for one patient and other underwent intersphincteric resection (ISR), both pT2 pN0 with TRG 2 and 3. Two patients had local regrowth, and one of them at 48 weeks underwent ISR. Other one had regrowth at 29 weeks and planned for surgery. In the entire cohort, organ preservation rate is 89.3%, local regrowth free rate (LRFR) is 89.3%, 2 Year PFS 82%, and 2 year OS is 91.7% using the Kaplan-Meier method. The W & W approach after cCR and ncCR to NACRT in LARC is acceptable with full compliance, feasible in LMICs in well-selected patients as a part of study group in a controlled research setting and early outcomes of this approach are similar to published literature.

Endoscopic Sinusotomy Using Needle Knife Technique for Treatment of H Pouch Sinus

J-shaped pouch is the most common pouch type used in restorative proctocolectomy (RP) with ileal pouch-anal anastomosis (IPAA) for medically refractory ulcerative colitis (UC). Due to anatomical difficulties, H-shaped pouch is occasionally performed during salvaging surgery for failed J-pouch. Here, we report the first case of an H-pouch complicated with a presacral sinus and successfully treated with needle knife sinusotomy (NKSi). A 62- year-old male with past medical history of UC, status post total colectomy with IPAA referred to our Pouch Center for progressive rectal pain, loose stool, and perianal swelling. Stool studies were negative including Clostridium difficile. A pouch stricture was found on barium enema. Flexible pouchoscopy revealed chronic fistula, abscess, and anastomotic stricture, for which he had exploratory laparotomy, lysis of adhesions, incision and drainage (I&D), extensive takedown of ileostomy, excision of the old J-pouch, excision of anastomotic stricture with creation of H-pouch with mucosectomy, handsewn anastomosis, and diverting loop ileostomy. Routine water-soluble contrast enema and abdominal computed tomography (CT) following surgery showed a pouch anastomotic leak. Pouchoscopy confirmed the deep sinus with thick walls. A wait and watch approach was tried for 2 months without antibiotics. However, repeat pouchoscopy showed a persistent pouch sinus. The decision was made to treat the sinus with endoscopic NKSi, followed by deployment of multiple endoclips along the edges of incised sinus wall. Patient's symptoms improved significantly following the procedure and he remained asymptomatic at 2 months post-procedure. A follow-up water-soluble contrast enema at 2 months showed normal appearing H pouch with no leak. Pouch sinus is a relatively infrequent complication after IPAA but has never been reported in patients with H-pouch IPAA. The ideal management is not well defined yet. In asymptomatic cases, patients are followed with repeat imaging to monitor for sinus healing. In cases where watchful waiting does not work, patients have habitually been treated with surgical interventions. We herein present the first case in the literature of an H-pouch complicated with anastomotic sinus successfully treated with NKSi. We suggest using NKSi as the preferred technique for H-pouch sinuses before performing any invasive surgical procedure.2053 Figure 1. No Caption available.

1209P - Immunotherapy in the immunodeficient: A treatment paradox?

Background: Patients with immunodeficiency are typically excluded from trials involving Immunotherapy, however they are at increased risk of developing malignancy. There is currently a lack of evidence to guide clinicians making difficult decisions in this cohort who have a theoretical risk of being unable to mount an adequate immune response. Methods: Patients diagnosed with Metastatic Melanoma treated with either single or dual immunotherapy regimes at University Hospital Southampton NHS Foundation Trust were identified through our electronic chemotherapy prescribing system. Those with a background of immunosuppressive states were analysed including high intensity chemotherapy or stem cell transplant for prior malignancy and HIV. Results: A total of 124 patients received Pembrolizumab monotherapy and 47 patients received Iplimumab with Nivolumab. Six patients were considered immunodeficient, including three patients treated with curative intent with intensive chemotherapy for prior lymphoma, one patient with HIV with undetectable viral load, one patient continuing on Ibrutinib treatment for Small Lymphocytic Lymphoma and one patient under a watch and wait approach for Chronic Lymphocytic Leukaemia. All patients in this group had any grade treatment related toxicity, with five experiencing severe grade 3-4 toxicity requiring hospitalisation. With a median follow up of 16.5 months no patients had reactivation of previous malignancy. Four out of six patients have had a complete radiological response and two patients had disease progression. Conclusions: In our cohort the majority of patients had a significant response to immunotherapy with toxicity managed without any long-term comorbidity. These patients were able to mount an anti-tumour immune response despite concurrent immunodeficiency and experienced an increased incidence of toxicity when compared with other patients treated at our centre. Despite the limitations of a small retrospective series our data would support offering immunotherapy even in the context of apparent immunodeficient states. Legal entity responsible for the study: University Hospitals Southampton. Funding: Has not received any funding. Disclosure: J. Longley: ESMO Travel Grant. I. Karydis: Travel, accommodations, expenses: Delcath Systems. M. Wheater: Consulting or advisory role: Roche, Novartis, MSD, Healthcare at Home; Travel, accommodations, expenses: MSD, Bayer, Bristol-Myers Squibb; Honoraria: Bristol-Myers Squibb, MSD Oncology, Pfizer, GlaxoSmithKline, Novartis, Delcath Systems; Research funding: Roche, GlaxoSmithKline, Novartis, MSD, Aveo, Bristol-Myers Squibb, Verastem, Merck Sharp & Dohme, Inovio Pharmaceuticals, BioNTech AG, Serametrix, Touchlight Genetics, Delcath Systems. C. Ottensmeier: Consulting or advisory role: Bristol-Myers Squibb, Merck Sharp & Dohme, Immatics; Travel, accommodations, expenses: Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Delcath Systems; Research funding: Bristol-Myers Squibb, Verastem, Merck Sharp & Dohme, Inovio Pharmaceuticals, BioNTech AG, Serametrix, Touchlight Genetics, Delcath Systems. All other authors have declared no conflicts of interest.

An Unusual Cause of Obscure Gastrointestinal Bleeding Unmasked by Video Capsule Endoscopy

Follicular lymphoma (FL) is the most common type of non-Hodgkin's lymphoma in the West, usually detected in lymph nodes. Gastrointestinal tract (GIT) is a common site of extra-nodal disease. We report a case of atypical GI-FL diagnosed as a consequence of investigations for microcytic anemia. A 73-year-old gentleman was referred for evaluation of iron-deficiency anemia, presumed GI source. Physical examination was grossly normal. Initial age-appropriate colonoscopy revealed a cecal hyperplastic polyp and non-bleeding internal hemorrhoids. Six weeks later, upper endoscopy for new-onset melena revealed grade C esophagitis, erosive gastritis, and single small angioectasia in anterior duodenal bulb, unlikely to account for the severity of blood loss. Duodenal biopsy was negative for celiac disease. Video capsule endoscopy (VCE) was performed for worsening anemia necessitating blood transfusion. Active oozing spot amongst an area of erythema, erosions, small ulcers and likely luminal narrowing and stricture was evident in the distal jejunum/proximal ileum. The capsule did not reach the cecum. Due to retained capsule and luminal stricture, CT enterography was performed. This revealed large anterior mediastinal, retroperitoneal, pelvic masses and extensive severe small bowel wall thickening, compatible with possible nodal and extra-nodal metastatic lymphoma. The capsule has since passed. Subsequent pelvic mass biopsy showed low-grade FL. Further staging including PET confirmed atypical involvement with most intense uptake in the mesentery, omentum and pleura, and extensive nodal and bone marrow involvement. GI-FL is a rare entity, generally affecting the small intestines. It is not always possible to determine the primary site of origin of GI-FL. It could either arise from extra-intestinal regions and present in the GIT at an advanced stage, or arise primarily in the GIT and disseminate to involve lymph nodes or other extra-intestinal sites. Optimal work-up and treatment plan is not well established. Endoscopic evaluation of the entire GIT and whole body PET are required for accurate staging. Based on the stage, treatment options include watch and wait approach, surgery, chemotherapy, radiotherapy, immune-radiotherapy or a multi-modal approach. Chemotherapy with rCHOP was initiated on our patient. Initially he responded to the regimen. Unfortunately, the disease turned aggressive shortly afterwards, and he subsequently transitioned to palliative care.1935_A Figure 1. Capsule endoscopy demonstrating edema, erosion, luminal narrowing and oozing in distal jejunum/proximal ileum.1935_B Figure 2. Active oozing from the erythematous, inflamed area with luminal narrowing narrowing in the distal jejunum/proximal ileum noted on capsule endoscopy.1935_C Figure 3. Capsule endoscopy demonstrating edematous, inflamed area in distal jejunum

Contact X-ray Brachytherapy as an Adjunct to a Watch and Wait Approach is an Affordable Alternative to Standard Surgical Management of Rectal Cancer for Patients with a Partial Clinical Response to Chemoradiotherapy

AimsEmerging evidence suggests that contact X-ray brachytherapy (CXB) may increase the clinical complete response rate and durability when administered after standard chemoradiotherapy in patients with rectal cancer. The addition of CXB in partial responders is therefore probably cost-effective. The affordability of widening access to CXB in the UK, however, has not been evaluated. Materials and methodsDecision analytical modelling with Monte Carlo simulation was used to evaluate long-term costs for the management of patients with rectal cancers who were given a CXB boost when a clinical complete response was not initially achieved following chemoradiotherapy in order to facilitate a watch and wait approach. A third-party payer (National Health Service) perspective was adopted, probabilistic sensitivity analysis was carried out and a scenario analysis was performed to investigate the effect of the number of referral centres and number of patients treated with CXB. ResultsWe estimate that 818 (95% confidence interval 628–1021) patients per year are eligible for CXB as an adjunct to a watch and wait approach in England and Wales. As this management is less costly than surgical management for each individual patient, the more patients treated, the more affordable the technology. Even if as few as 125 patients are treated nationally in 15 centres, the cost of implementing this technology would be less than £4 million. If the average number of patients treated in each centre is 30, this technology would be cost saving within 5 years. ConclusionsThe cost of CXB is not prohibitive according to the National Institute for Health and Care Excellence threshold for implementation of new technology and may even be cost saving within 5 years compared with standard surgical management, depending on the uptake of the technology and the number of referral centres.

UTIs in older people: the programme reducing unnecessary prescribing

Pioneering nurse Jo McEwen is leading the way in antimicrobial stewardship, using a watch and wait approach to cut inappropriate antibiotic prescribing and improve care

Watch and Wait Approach for Inactive Echinococcal Cyst of the Liver: An Update.

Human cystic echinococcosis (CE) is a chronic, complex and neglected infection causing severe disease in humans. Hepatic CE cysts are detected and classified mainly by using ultrasound. Expert opinion and published data suggest that uncomplicated inactive liver cysts do not require treatment and only need to be monitored over time ("Watch and Wait"). Here we update our findings as published in 2014 on the "Watch and Wait" approach applied to inactive, asymptomatic cysts of the liver to keep the medical community informed. Clinical data of patients who accessed the World Health Organization Collaborating Center for CE at the University of Pavia-San Matteo Hospital Foundation from January 1991 to October 2017 were analyzed. Inclusion criteria were presence of one or more inactive uncomplicated cysts in the liver (CE4 or CE5), without any history of previous treatment, and an ultrasound-based follow-up of at least 24 months. Fifty-three patients with 66 inactive cysts fulfilled the inclusion criteria. Of these, 11 patients are newly described here; 37 were part of our previously described cohort and the follow-up for 17 of them was further extended; and five were excluded from the previously published analysis as their follow-up was too short, but could be included now. Without the need for treatment and without development of complications, 98.5% of cysts remained inactive over time. In only one patient (1.9% of patients), a reactivation of one cyst (1.5% of cysts) was observed.

Chemolysis of a Uric Acid Stone in a Horseshoe Kidney

Chemolysis of kidney stone is not unheard of. However, to our knowledge, there is no previous report of chemolysis of a kidney stone in a horseshoe kidney. We report the first ever case of chemolysis of a stone in a horseshoe kidney. As part of his visible haematuria workup 4 years ago, a 66-year-old gentleman with a history of gout was found to have a horseshoe kidney. In early 2017, he was seen in the urology clinic with some non-specific abdominal pain without a recent history of visible haematuria, lower urinary tract symptoms, and urinary tract infections. His CT KUB (computed tomography of kidneys, ureters and bladder), revealed a 1.3cm stone in his horseshoe kidney [Figure 1 and 2]. At the same time, his CT KUB has also picked up some retroperitoneal lymphadenopathy in the abdomen and pelvis which were suspicious of lymphoma. His serum uric acid level was noted to be normal. Subsequently, he underwent a laparoscopic right iliac lymph node biopsy which confirmed nodal marginal zone non-Hodgkin's B-cell lymphoma. He was reviewed by the haematology team and they decided to adopt a watch and wait approach to his disease with quarterly CT CAP (computed tomography of chest, abdomen and pelvis) scans. During this period of time, he had several gout attacks and he was started on allopurinol i.e. 100mg once a day. He also considerably increased his daily fluid intake. 6 months after his initial CT KUB, he was found to be completely stone free on his CT scan [Figure 3 and 4].

A two‐dimensional, two‐level framework for achieving corporate sustainable development: Assessing the return on sustainability initiatives

AbstractSustainability studies in operations management have reported the positive effects of lean, green and social management systems on various dimensions of a firm's sustainability performance. However, despite its importance and relevance, the time dimension of sustainability has not been systematically considered. This paper recategorizes the well‐identified sustainability initiatives based on a time dimension and empirically validates the categorization. Structural equation modeling analyses were performed using data collected from 284 Chinese automotive firms. The results suggest that various lean and reactive green practices can be categorized as “short‐term sustainability initiatives” because the effects of implementing these practices can be seen in a short time. Specifically, the benefits of implementing short‐term sustainability initiatives can be further strengthened and reinforced in the long run by implementing corporate social responsibility (CSR) practices. In addition, our findings demonstrate that to fully realize the potential associated with CSR practices, firms need to be orientated to the long term and adopt a wait and watch approach.