Partial Clinical Response Research Articles

P0792 Remission rates in Complex Perianal Fistulizing Crohn's Disease – Real-life experience of a tertiary reference center

Abstract Background The treatment of complex perianal fistula (cPF) in Crohn’s Disease (CD) requires an integrated and multidisciplinary approach (1) This phenotype affects up to a third of CD patients (2,3) and significantly harms their quality of life (4). This study aims to review the experience of a tertiary reference center and identify prognostic factors related to non-response to treatment. Methods Adult patients with CD who underwent surgery for cPF, in a tertiary reference center, between 2015 and 2023 were retrospectively reviewed. Extracted data included baseline demographic data, clinical recurrence of perianal disease, and resolution of perianal disease. Cases were stratified according to clinical response to treatment of perianal disease after surgery: complete clinical response (clinical remission), partial clinical response, clinical nonresponse or clinical recurrence. Results Seventy-nine patients (50.6% male) were included; the average age was 28 years (Q1=21 and Q3=38). Median follow-up of 85 months (interquartile range, 37-124); the multidisciplinary team discussed all of them. At the time of first surgery, 53.2% of patients had trans-sphincteric cPF, 22.8% had supra-sphincteric cPF, and 15.2% had rectovaginal cPF. In 88.6% of patients, the first procedure was seton placement. All but two patients were treated with 1 to 4 biologic drugs. The two patients treated with mesenchymal stem cells transplantation achieved a complete clinical response at 24 weeks, maintained at 52 weeks of follow-up. Female sex was a protective factor for nonresponse to treatment, and supra-esfincteric fistula was factor associated with the risk of nonresponse or recurrence. At end of follow-up, 78.5% of patients had a complete or partial response, and 21.5% had a nonresponse or a recurrence. Due to perineal destruction 3 patients required an ostomy, and the other 3 a proctectomy. Conclusion This real-life study showed that a multidisciplinary approach, including surgical intervention, can completely heal Crohn's disease perianal fistula in more than seventy-eight percent of patients. Supra-esphincteric fistula was a risk factor for worse disease outcomes, and female sex was a protective factor for nonresponse.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response. An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism. Clinical data at baseline and 6-12 months post-treatment were collected from patients with primary aldosteronism who started targeted medical treatment between 2016 and 2021 at 28 participating centres. Consensus was reached for defining complete, partial, or absent biochemical or clinical response. Of 1258 patients (with a mean age of 52 years [SD 11·5] and of whom 610 [48·5%] were female and 648 [51·5%] were male), 1057 (84·0%) had biochemical outcome data (559 [52·9%] had a complete biochemical response). The median daily dose of spironolactone was significantly higher for those with a complete biochemical response than for those without (40 mg [IQR 25-50] vs 25 mg [20-50]; p=0·011). Of the 1248 patients with clinical outcome data, 228 [18·3%] had a complete clinical response whereas 227 (18·2%) had an absent response. Patients with a complete clinical response were more likely than those with partial or absent clinical response to be women (OR 2·099, 95% CI 1·485-2·968; p<0·001), require lower doses of antihypertensive drugs at baseline (0·687, 0·603-0·782; p<0·001), and were less likely to have microalbuminuria or left ventricular hypertrophy (0·584, 0·391-0·873; p=0·009). The Primary Aldosteronism Medical Treatment Outcome (PAMO) criteria represent an internationally developed outcome standard that can guide clinical practice and research into primary aldosteronism. Efforts to optimise treatment intensity and minimise factors associated with an absent treatment response are needed to improve patient outcomes. None. For the Chinese (simple), Chinese (complex), Japanese, Korean, German, French, Spanish, Dutch, Swedish, Slovenian, Polish, Italian and Russian translations of the abstract see Supplementary Materials section.

Photodynamic Therapy in Acne Vulgaris: A Systematic Review

Acne is a multifactorial disorder of the pilosebaceous unit. Photodynamic therapy (PDT) is an energy-based treatment shown to be safe in acne vulgaris, although the mechanism of action of PDT in acne is incompletely understood. This review summarizes the clinical features of and treatment efficacy in acne patients treated with PDT. A systematic review of Medline, Embase, and the Cochrane Database of Systematic Reviews was conducted. Title, abstract, full-text screening, and data extraction were completed using Covidence. Studies reporting the use of PDT in patients with acne were included while clinical features and treatment responses were extracted. Treatment outcomes were scored as complete response, partial response, and no response. After screening a total of 1122 studies, 82 studies met the inclusion criteria, representing 56 prospective studies, 25 randomized controlled trials, and 1 retrospective study. Results representing 4340 patients with acne (mean age 24.4 years; 52% females) treated with PDT are summarized. Overall, 2154 (50%) participants underwent aminolevulinic acid PDT, 452 (10%) participants underwent methyl aminolevulinate PDT, 28 (&lt;1%) participants underwent daylight PDT, and 1706 (39%) underwent other modalities of PDT. The average follow-up period after study completion was 3 months, ranging from 2 weeks to 13 months. A partial response was observed in treated patients with outcome measures including clinical response, lesion count, pain, recurrence, and patient satisfaction. This systematic review provides preliminary data summarizing the clinical features and treatment efficacy in patients with acne treated with PDT. Our results suggest a partial clinical response when using PDT to manage acne. Future studies should focus on standardizing study protocols and drawing direct comparisons between PDT and other modalities for acne treatment.

Personalized Medicine in Histiocytic Disorders: Novel Targets in Patients Without MAPK Alterations.

BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective. We describe three patients with histiocytic disorders who have novel non-MAPK pathway alterations. These alterations were studied through genomic and in silico analyses when applicable, then treated with off-label medications rationally selected on the basis of genomic alterations. Patient 1 had rapidly progressive ECD involving the CNS. A CSF1R in-frame deletion (p.S560_P566del) was identified, and in silico modeling predicted a gain-of-function mutation. This alteration was targeted with pexidartinib, which led to a clinical complete response (CR) within 2 months, and a partial response (PR) on imaging after 3 months. After 15 months, the disease became resistant to pexidartinib and transformed to histiocytic sarcoma. Patient 2 has skin-only involvement of a xanthogranuloma disorder. A KIF5B-FGFR1 fusion was identified on RNA sequencing and targeted with pemigatinib. At 24 months of follow-up, she remains in a clinical PR. Patient 3 has ECD involving the bone marrow, gastrointestinal tract, and subcutaneous tissues. A MEF2C-FLT3 fusion was identified and targeted with sorafenib. He achieved a clinical CR and radiographic PR within 3 months, which has continued for 30 months. We report three patients with histiocytic disorders harboring novel alterations who had sustained responses to off-label kinase inhibitors specific to their histiocytic disorder. Pathogenic variants outside of the MAPK pathway, including variants of unknown significant, may be targeted with readily available small molecules.

Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Insights from the Western Australian Context.

Recent studies have associated total neoadjuvant therapy (TNT) with better treatment adherence, decreased toxicity, improved complete clinical response and anal sphincter preservation rates in patients with locally advanced rectal cancer (LARC). However, real-world experience with TNT in the management of LARC remains limited. This study aimed to evaluate the efficacy and safety outcomes of TNT for LARC in Western Australia. Patients with LARC (cT2-4 and/or cN1-2) who underwent induction chemotherapy followed by neoadjuvant chemoradiotherapy or neoadjuvant chemoradiotherapy followed by consolidation chemotherapy, followed by surgery were recruited from two hospitals in Western Australia. Efficacy outcomes assessed included clinical response (complete, partial, no response), and pathologic complete response (pCR) rate, R0 resection rate, and R1 resection rate were evaluated. Those patients who achieved clinical complete response following TNT were given the option of active surveillance. The safety and tolerability of TNT were assessed. 32 patients with LARC were treated with TNT. In total, 17 patients (53%) received chemoradiotherapy followed by consolidation chemotherapy and 15 patients (47%) received induction chemotherapy followed by chemoradiotherapy. Nine (28%) of the patients with LARC treated with TNT had a complete clinical response, twenty-one (66%) patients had a partial clinical response, and two (6%) patients had no response to TNT. Of the 32 patients, 27 (84%) underwent surgery. There was a 100% R0 resection rate. The pCR rate was 15%. pCR, clinical response, and the R0 resection rate were similar between the two TNT regimens. TNT was well tolerated, with the majority of patients (88%) completing the chemotherapy course with grade 1 and 2 adverse effects. In conclusion, TNT emerges as a promising approach for the management of LARC. However, further research is warranted to refine the optimal TNT protocols, determine its long-term outcomes, and identify patient populations who would benefit the most from this innovative therapeutic strategy.

7787 Primary Aldosteronism Medical Treatment Outcomes (PAMO): An International Consensus on Outcome Assessment Criteria and Multicentre Study

Abstract Disclosure: J. Yang: None. J. Burrello: None. J. Goi: None. T.A. Williams: None. W.F. Young: Consulting Fee; Self; Arena Pharmaceuticals, Inc.. Other; Self; Crinetics Pharmaceuticals. P.J. Fuller: None. P. Investigators: None. Primary aldosteronism (PA) is the most common endocrine cause of hypertension. Mineralocorticoid receptor antagonists, at adequate doses, lower blood pressure and cardiovascular risk in patients with PA. However, there is a lack of a standardized approach to medical therapy and subsequent outcomes assessment. We aimed to: 1) establish criteria for assessing outcomes of targeted medical treatment of PA, and 2) evaluate outcomes using these criteria across an international cohort. A panel of 31 PA experts from 31 centres across four continents used the Delphi method, including three rounds of online questionnaires, to reach consensus. Clinical data were then collected from consecutive patients with PA who started targeted medical treatment between 2016 and 2021 at the participating centres. Consensus was reached for six outcomes, including complete, partial, or absent biochemical response, and complete, partial, or absent clinical response. “Complete biochemical response” was defined as “correction of hypokalemia without potassium supplementation, and normalization of plasma renin activity or concentration”; while “absent biochemical response” was defined as “persistent hypokalemia and/or persistently suppressed or low plasma renin activity or concentration without change from baseline”. “Complete clinical response” was defined as “normal blood pressure without additional antihypertensive medications”; while “absent clinical response” was defined as “the same or increased blood pressure compared to before targeted treatment with same or more antihypertensive medications, not counting targeted therapy”. Of 1483 patients (mean age 52y, 48% female) from 28 centers, 232 (16%) had a complete clinical response, and 719 (49%) had a complete biochemical response at the most recent follow-up (median 29 months after treatment initiation). Compared to those with partial or absent clinical response, patients with complete clinical response had a significantly higher proportion of women and lower proportion with diabetes, stroke or left ventricular hypertrophy. They also had a significantly shorter duration of hypertension, lower BMI, higher eGFR and lower defined daily dose of antihypertensives at baseline. In contrast, these differences were not observed in those with a complete, partial or absent biochemical response. The defined daily dose of targeted therapy did not differ across the various response categories. In conclusion, we have established an international expert consensus for standardized criteria to evaluate the response to targeted medical treatment of PA, facilitate comparisons of outcome data and guide clinicians who manage PA. In a retrospective international cohort, less than half of medically-treated patients reached the established biochemical treatment targets. Further work is needed to increase the rate of complete response. Presentation: 6/3/2024

Assessment of Radiotherapy as a Standalone Treatment Following Neoadjuvant Chemotherapy in Nonmetastatic Breast Cancer: A SEER Database Analysis.

Traditional breast cancer management involves surgery followed by systemic therapies. However, advancements in neoadjuvant chemotherapy (NACT) raise questions about the necessity of surgery in cases with an excellent response to NACT. This study investigates the outcomes of radiotherapy without surgery in selected patients with nonmetastatic breast cancer after a complete or substantial response to NACT. A retrospective study was conducted using the SEER database, reviewing records from 2010 to 2020 for patients with nonmetastatic breast cancer who received NACT, associated with a clinical response, followed by radiotherapy alone. The population included 123 patients, stratified into complete clinical response (cCR) and non-cCR (partial or unspecified clinical response) cohorts. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier and Cox proportional hazards models. The median follow-up was 41 months. Among the patients, 17 (13.82%) achieved cCR. The 5-year OS and CSS for the entire cohort were 65.8% and 71%, respectively, with the cCR group achieving 100% rates for both. Age above 60 and larger tumor size (T3 to T4) were associated with lower OS. The non-cCR group showed a 5-year OS of 61.5% and CSS of 67.1%. This study indicates that omitting surgery in patients with a cCR to NACT may be feasible, as evidenced by this subgroup's 100% OS and CSS rates at 5 and 10 years. These promising results support further research into less invasive breast cancer management. However, prospective studies must validate these findings and identify suitable patients for nonsurgical approaches.

Efficacy of Methotrexate and Anti-TNF Combination Therapy in Adults with Refractory Crohn's Disease.

Biological medications have played a significant role in maintenance therapy for Crohn's disease (CD), but some cases become refractory to these agents. Methotrexate (MTX) appears to be a cost-effective and readily available drug for enhancing the effectiveness of maintenance therapy when used in combination with anti-tumor necrosis factor (anti-TNF) therapy in such cases. However, its effectiveness is still to be established. We aimed to assess the efficacy of MTX and anti-TNF combination therapy in patients with refractory CD. A retrospective cohort study was conducted on adult patients with CD who were refractory to anti-TNF therapy and were initiated on weekly intravenous MTX in addition to the anti-TNF therapy. These patients were then followed up for over a year. The primary outcome measured was the clinical response to treatment, based on the Harvey-Bradshaw Index. The secondary outcomes included assessing the adverse events and complications of MTX therapy. Of 70 patients, 44 were included in the final analysis. Among them, 30 patients (68.2%) achieved complete remission, four patients (9.1%) had a partial clinical response, and 10 patients (22.7%) required surgery. The adverse events and complications of MTX therapy were mild and infrequent (9.1%). None of the demographic or clinical factors were significantly associated with response to treatment (P>0.05). Combining MTX with anti-TNF therapy appears to be an effective and safe treatment for patients with Crohn's disease, particularly those with severe disease who are less responsive to monotherapy. However, further studies are needed to confirm these findings.

Hypophosphatemic Rickets as a Key Sign for the Diagnosis of Hereditary Tyrosinemia Type 1: Case Reports and Narrative Review of the Literature.

Hereditary tyrosinemia type 1 (HT-1) is an inborn error of metabolism caused by a defect in tyrosine (tyr) degradation. This defect results in the accumulation of succinylacetone (SA), causing liver failure with a high risk of hepatocarcinoma and kidney injury, leading in turn to Fanconi syndrome with urine loss of phosphate and secondary hypophosphatemic rickets (HR). HT-1 diagnosis is usually made in infants with acute or chronic liver failure or by neonatal screening programs. HR is rarely described in the literature as the main feature or chief complaint of patients with HT-1. Clinical cases: We present three children who presented signs of HR during infancy. Patient 1 had early liver dysfunction, leading to a quick diagnosis of HT-1. Patients 2 and 3 started conventional therapy for HR (calcitriol and oral phosphate) with partial clinical response. Later, both developed liver dysfunction, and patient 3 presented neurological symptoms (porphyria-like crises). An HT-1 diagnosis was made using tandem mass spectrometry, which confirmed high plasma levels of SA and tyr. After diagnosis, all started treatment with a specific diet and nitisinone with prompt recovery and a quick remission of clinical signs of HR, being able to discontinue their conventional rickets therapy successfully. Conclusion: We present three patients with HT-1 whose main complaint was HR. It is important to know the main features of this metabolic disorder and have a high index of suspicion when we follow-up children with HR, especially if they are not responding to conventional therapy or develop liver dysfunction.

A study of the assessment of pathological response to neoadjuvant chemotherapy in patients with breast cancer

Abstract: BACKGROUND: Neoadjuvant chemotherapy therapy ( NACT) has emerged as an integrated therapeutic approach to treat locally advanced breast cancer in order to down stage the tumour and to assess tumour response to chemotherapy. The aims of this study were to estimate the incidence of complete and partial pathological response in patients undergoing NACT for breast cancer and to evaluate the clinico pathological parameters associated with pathological response. MATERIALS AND METHODS: The study included breast cancer specimens from patients who had received NACT. The pathological response to NACT was assessed by the AJCC protocol and the morphological features associated with NACT were recorded. The clinicopathological parameters associated with complete pathological response were also studied. The association between the clinicopathological paramaters and pathological response was studies using Chi square and Fisher exact tests. RESULTS: There were a total of 50 women who underwent surgery for breast cancer following NACT. The mean age was 56.5 years. The majority (59.1%) belonged to stage IIIB followed by Stage III A ( 30.6%). 73.4% of cases showed clinical partial response, 14.2 % showed no response and 12.2 percent showed Pathological Complete Response (pCR). ER and PR negative and Her 2 positive status were the parameters significantly associated with pCR. CONCLUSIONS: Pathological evaluation is the most reliable method to assess response to NACT in breast cancer patients which may further influence management decisions. This study showed a much lower frequency of pCR when compared to other Indian studies. It is recommended that all patients who are treated with NACT undergo prior core needle biopsy with hormone receptor and Her 2 testing as they may have a bearing on pCR.

The Efficacy and Safety of Endoscopic Balloon Dilatation in the Treatment of Functional Post-Sleeve-Gastrectomy Stenosis

Background and Objectives: Functional gastric stenosis, a consequence of sleeve gastrectomy, is defined as a rotation of the gastric tube along its longitudinal axis. It is brought on by gastric twisting without the anatomical constriction of the gastric lumen. During endoscopic examination, the staple line is deviated with a clockwise rotation, and the stenosis requires additional endoscopic manipulations for its transposition. Upper gastrointestinal series show the gastric twist with an upstream dilatation of the gastric tube in some patients. Data on its management have remained scarce. The objective was to assess the efficacy and safety of endoscopic balloon dilatation in the management of functional post-sleeve gastrectomy stenosis. Patients and Methods: Twenty-two patients with functional post-primary-sleeve-gastrectomy stenosis who had an endoscopic balloon dilatation between 2017 and 2023 were included in this retrospective study. Patients with alternative treatment plans and those undergoing endoscopic dilatation for other forms of gastric stenosis were excluded. The clinical outcomes were used to evaluate the efficacy and safety of balloon dilatation in the management of functional gastric stenosis. Results: A total of 45 dilatations were performed with a 30 mm balloon in 22 patients (100%), a 35 mm balloon in 18 patients (81.82%), and a 40 mm balloon in 5 patients (22.73%). The patients’ clinical responses after the first balloon dilatation were a complete clinical response (4 patients, 18.18%), a partial clinical response (12 patients, 54.55%), and a non-response (6 patients, 27.27%). Nineteen patients (86.36%) had achieved clinical success at six months. Three patients (13.64%) who remained symptomatic even after achieving the maximal balloon dilation of 40 mm were considered failure of endoscopic dilatation, and they were referred for surgical intervention. No significant adverse events were found during or following the balloon dilatation. Conclusions: Endoscopic balloon dilatation is an effective and safe minimally invasive procedure in the management of functional post-sleeve-gastrectomy stenosis.

Clinicopathological correlation of patients with lupus nephritis: Data from a tertiary center in Saudi Arabia.

Systemic lupus erythematosus mainly affects young women, and approximately half of systemic lupus erythematosus patients develop lupus nephritis (LN). However, data on the types and remission rates of LN in Saudi Arabia are limited. Therefore, we aimed to highlight the LN remission rates in our population. A retrospective record review was conducted between January 2007 and December 2020 in a tertiary center in the western region of Saudi Arabia to determine the remission rates among patients with biopsy-proven LN who met the EULAR\ACR 2019 classification criteria. We identified 59 patients with biopsy-proven LN, mostly in young women. The common histopathological pattern was Class IV LN in 26 patients (44%). Three induction protocols were identified, along with systemic steroids: the high-dose cyclophosphamide protocol in 21 patients (35.6%), low-dose protocol in 4 patients (6.8%), and mycophenolate mofetil (MMF) in 41 patients (69.5%). Partial response, defined as the reduction of the 24-hour proteinuria by 25% at 3 months and 50% at 6 months, was achieved in 18 patients (33.3%) at 3 months and decreased to 13 patients (24.1%) at 6 months. Complete clinical response, defined as 24-hour urinary protein between 500 and 700 mg at 12 months, was achieved in 44 patients (81.5%). Complete remission was higher among patients with Class IV LN (64.4%). The achievement of partial clinical response at 3 months was significantly lower among patients with hypertension (P = .041). This study presented the LN remission rates in a single center in Saudi Arabia. Similar to previous studies, Class IV LN were the most common histopathological finding in this study. Complete remission at 12 months was achieved in 44 (81%) patients. Delayed remission is associated with hypertension at the time of LN diagnosis.

The Efficacy of Trigger Site Surgery in the Elimination of Chronic Migraine Headache: An Update in the Rate of Success and Failure.

Migraine headache (MH) is a prevalent neurovascular disorder that affects approximately 15% of the global population. They are more common in women and typically affect young and middle-aged individuals. Chronic MH is characterized by headaches occurring on ≥15 days per month for over three months. While only 5% of MHs are refractory, about 20%-50% do not respond to pharmacologic treatments. As a result, surgical interventions have emerged as an alternative method to eliminate MH since 2000 AD. These surgical treatments primarily target the peripheral mechanisms of MH, focusing on common trigger sites. Migraine surgery involves neurolysis of sensory branches of trigeminal and occipital nerves that supply the face and back of the head. Numerous clinical studies conducted between 2000 and 2021 have extensively described surgical interventions and their prognostic outcomes. After surgery, up to 80% of patients reported complete elimination of headaches, while 20%-35% experienced no relief. The failure to achieve complete elimination of MH can be attributed to various factors. The most common reason for a partial clinical response is the failure to identify all trigger sites or inadequate surgery on the trigger sites. In this review, we aim to provide an overview of current surgical interventions for MH at different trigger sites, including recent updates, success and failure rates, and potential causes of failure.

Long Term Outcomes in Idiopathic Inflammatory Myositis: An Observational Epidemiologic Study over 15 Years.

We report a longitudinal observational cohort of idiopathic inflammatory myositis (IIM) focusing on the long-term clinical outcome and associated parameters. IIM patients were classified as per Bohan and Peter criteria. In those with ≥ 24 months of follow-up; the treatment response, functional outcomes, and damage at last follow-up were recorded. Complete clinical response and clinical remission as defined by Oddis et al., was used to define outcomes at last follow-up. The cohort consists of 175 patients, mean age 40.9 (+12.6) years, M:F 1:3.3; and the major subsets were dermatomyositis (44.6%), overlap myositis (25.7%), antisynthetase syndrome (6.3%), polymyositis (14.3%), and juvenile DM/OM (8.6%). Ninety-four patients have followed up for 24 months or more, with the median (IQR) of 65(35,100.7) months. Of them, 74.1% and 11.8% had complete and partial clinical responses respectively at the last follow-up. In our cohort 40.2% were off-steroids and 13.8% were in clinical remission at the last follow-up. Complete clinical response was associated with better functional outcomes and lesser damage as determined by HAQ-DI of 0[OR10.9; 95%CI (3.3,160)], MRS [OR 3.2; 95%CI (1.4,7.3)] and lesser MDI [OR 1.7; 95% CI (1.1,2.7)] respectively as compared to partial response (unadjusted analysis). Baseline parameters and IIM subsets did not significantly influence the functional outcome and damage. The mortality rate in our cohort is 24/175 (13.7%), the disease-specific mortality rate being 9.1%. Large majority of deaths were early, associated with active disease. We report good long-term outcomes in all major myositis subsets. Partial clinical response to treatment is associated with worse functional outcomes and damage accrual. Death occurs early in association with active disease.

Lateral Pelvic Nodal Management and Patterns of Failure in Patients Receiving Short-Course Radiation for Locally Advanced Rectal Cancer.

Management of lateral pelvic lymph nodes in locally advanced rectal cancer is controversial, with limited data indicating the optimal approach. Additionally, no data exists regarding treatment of lateral nodes in the setting of short course radiation and nonoperative intent. We evaluate a novel approach incorporating simultaneous integrated boost to suspicious lateral nodes. This was a retrospective study. This study was conducted at a large, tertiary referral center. Patients treated with radiation and consolidation chemotherapy were included. All primary tumors were biopsy confirmed and disease-staged with pelvic magnetic resonance imaging. Primary tumors were biopsy proven and staged with pelvic magnetic resonance imaging. A subset of lateral pelvic lymph nodes patients received simultaneous integrated boost to 35 Gy in 5 fractions. Then, chemotherapy was administered with the majority receiving mFOLFOX (modified folinic acid, fluorouracil, and oxaliplatin). Clinical partial response required total mesorectal excision. Patterns of failure and survival analyses by subgroup were assessed. Outcomes based on receipt of radiation were compared across node status. Between January 2017 - January 2022, 155 patients were treated with short course and chemotherapy with 121 included in final analysis. Forty-nine percent underwent nonoperative management. Median follow-up was 36 months and median age was 58 years. Thirty-eight patients (26%) had positive lateral pelvic lymph nodes. Comparing lateral node status, progression-free survival was significantly worse for patients with positive disease (p < 0.001) with a trend for worse overall survival. Receipt of nodal boost in patients with lateral nodes resulted in meaningful locoregional control. Nodal boost did not contribute to additional acute or late GI toxicity. Limitations included retrospective nature and lack of lateral nodes pathology; however, thorough radiographic review was performed. Lateral node positive rectal cancer is correlated with worse oncologic outcomes and higher locoregional failure. Boost to clinically positive lateral nodes is a safe approach in the setting of short course and in those receiving nonoperative intent.

Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children

BackgroundChronic active Epstein–Barr virus infection (CAEBV) and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however, most patients relapse and/or progress. Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy; however, there are risks of transplantation-associated complications. Currently there is no standard treatment for CAEBV and EBV-HLH. Programmed death protein 1 (PD-1) inhibitors have achieved a high response in many EBV-related diseases. Sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) disrupts the interaction between PD-1 and its ligand, leading to T cell reinvigoration.MethodsA retrospective analysis was performed on three children with CAEBV or EBV-HLH in the Children’s Hospital of Soochow University between 12 December 2020 and 28 November 2022. The efficacy of sintilimab was evaluated.ResultsThree patients, including two males and one female, were analyzed. Among them, two children were diagnosed with CAEBV with intermittent fever for more than four years, and one child was diagnosed with EBV-HLH. After sintilimab treatment and a mean follow-up of 17.1 months (range 10.0–23.3 months), patients 1 and 3 achieved a complete clinical response and patient 2 achieved a partial clinical response. All three children showed a > 50% decrease in EBV-DNA load in both blood and plasma. EBV-DNA copies in sorted T, B, and NK cells were also markedly decreased after sintilimab treatment.ConclusionOur data supported the efficacy of PD-1 targeted therapy in certain patients with CAEBV and EBV-HLH, and suggested that sintilimab could provide a cure for these diseases, without HSCT. More prospective studies and longer follow-up are needed to confirm these conclusions.

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

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

Pathological complete response and survival of HER2-positive invasive breast cancer following docetaxel, carboplatin, and trastuzumab neoadjuvant therapy: a Vietnamese experience

Introduction. Neoadjuvant chemotherapy for HER2-positive breast cancer consists of a chemotherapy regimen plus trastuzumab with or without pertuzumab. The use of trastuzumab has been shown to improve pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). Purposes: To evaluate the efficacy and safety of neoadjuvant docetaxel, carboplatin, and trastuzumab (TCH) in the treatment of HER2-positive breast cancer in Vietnamese patients. Material and methods. This retrospective study reviewed stage II–III HER2-positive breast cancer patients who received neoadjuvant docetaxel, carboplatin, and trastuzumab (TCH) at the Vietnamese National Cancer Hospital. The primary endpoint was the pCR rate which was defined as the absence of invasive tumor in the breast and axillary nodes (ypT0/is, ypN0). The secondary endpoints were DFS, OS, and toxicities. Results. The complete and partial clinical response of 51 patients were 33.3% and 58.8%, respectively. The pCR rate was 41.2%; there was a significantly higher response in cT1-2 patients compared to cT3-4 ones (61.1% vs. 39.3%, p = 0.033). Three-year estimated DFS and OS rates were 81.3% and 93.0%, respectively. Treatment was generally well tolerated. Grade 3/4 neutropenia and anemia were uncommon (21.6% and 7.8%). No symptomatic cardiac dysfunction occurred. Conclusions. Neoadjuvant TCH, non-anthracycline chemotherapy with single anti-HER2 regimen achieved high efficacy, with a good pCR rate and favorable tolerability in stage II or III HER2-positive breast cancer patients.

Predictors of successful outcome after adrenalectomy for unilateral primary aldosteronism.

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

PD04 Real-life experience of Scottish patients with idiopathic solar urticaria

Abstract We conducted a retrospective study to characterize our most recent cohort of patients with idiopathic solar urticaria (SU), to compare with our previous findings (Beattie PE, Dawe RS, Ibbotson SH, Ferguson J. Characteristics and prognosis of idiopathic solar urticaria: a cohort of 87 cases. Arch Dermatol 2003; 139:1149–54). We analysed data derived from our in-house database and paper and electronic records of patients with SU seen through the Scottish Photobiology Service between 2003 and 2022. Eighty-four patients with SU were seen in this period, 57 (68%) women and 27 (32%) men. Twenty-nine (35%) had a single consultation/phototesting and 55 (65%) had follow-up assessments. The average age of onset was 37 years, with the average age of diagnosis being 41 years, with delays from symptom onset to diagnosis ranging from 6 months to 24 years. Importantly, 20 (24%) patients self-reported systemic symptoms, most commonly fatigue, dizziness and nausea. Of 61 patients using antihistamines before diagnosis, 31 (51%) reported benefit. Of patients who tried sunscreens, 31 of 65 (48%) reported benefit. On monochromator phototesting, sensitivity predominantly involved the ultraviolet (UV)A waveband (335–400 + 27 nm in 55%), extending into the visible spectrum (&amp;gt; 430 + 27 nm) in 44% and UVB waveband (305 + 5 nm) in 1%, consistent with previous reports of predominant UVA/visible light dependency in SU. On review of follow-up data, we analysed the fold benefit in minimal urticaria dose (MUD) from testing on H1 antihistamines alone, H1 and H2 antihistamines combined and the addition of montelukast. Most (65%) responded with a more than twofold improvement in MUD after a single dose of H1 antihistamine, with only 35% not responding. Increasing the dose of H1 antihistamine did not provide notable additional benefit. There was a suggestion of improved responses by the addition of an H2 antagonist (in 76% vs. 66% with H1 antagonist alone), but this was not statistically significant (P &amp;gt; 0.05). No additional improvement in threshold sensitivity (MUD) was observed by the addition of montelukast. Small numbers of patients used other treatments such as photo(chemo)therapies and systemic immunosuppressants, and these were found to be of limited benefit. Since 2011, we have used omalizumab for patients with treatment-resistant SU. Of the current cohort, 13 received omalizumab, with 62% reporting a good clinical response and a further 15% a partial clinical response. Phototesting in these patients showed complete abolition of photosensitivity or excellent responses (more than fivefold increase in MUD) in 73%, demonstrating the efficacy of omalizumab in recalcitrant SU. Given the systemic features reported by some patients with SU, this supports a management approach, which includes systemic immunomodulation as a potentially effective option.