Organ Preservation Therapy Research Articles

Real-world study of urine-based NGS liquid biopsy in organ preservation therapy of muscle-invasive bladder cancer (MIBC).

Real-world study of urine-based NGS liquid biopsy in organ preservation therapy of muscle-invasive bladder cancer (MIBC).

Incidence and Management of Pharyngo Cutaneous Fistula Following Total Laryngectomy - A Single Institutional 10 Years Experience.

Pharyngocutaneous fistula (PCF) is a common postoperative complication in patients undergoing laryngectomy. Many studies have focused on the predisposing factors and their treatment, but there is still controversy on how to identify high-risk patients.PCF is associated with delay in adjuvant treatment, prolonged hospital stay, and the requirement for additional surgical procedures. The increased incidence of post-laryngectomy PCF in the modern era of organ preservation therapy has driven considerable efforts to develop techniques to avoid and treat this complication. The study aims to analyze the incidence, predisposing factors, management, and outcome of PCF in post laryngectomy patients. We reviewed retrospectively the medical records of 72 patients who underwent total laryngectomy during the period from 2013 to 2022 at our institute. Details regarding age, gender, tumor site, comorbidities, radiotherapy, chemotherapy, duration of nasogastric tube feeding, the incidence of PCF and its management, and length of hospital stay. In our analysis of 72 patients, with 38 undergoing upfront laryngectomy and 34 salvage laryngectomy post-chemoradiation, we observed a 23% incidence of Pharyngocutaneous Fistula (PCF). Our univariate analysis revealed that low pre-op albumin levels and advanced stage significantly increased the risk of PCF. Specifically, PCF occurred in 16% of upfront laryngectomy patients and increased to 32% in salvage laryngectomy patients, though there was no significant association with pre-operative radiotherapy (RT).Among PCF cases, those from upfront laryngectomy had a mean onset time of 12 days, while salvage laryngectomy cases had a mean onset time of 8 days. The majority of PCF cases (64%) were managed conservatively, with 11% resolving through secondary suturing and 25% requiring surgical repair using local flaps. Notably, 80% of upfront laryngectomy PCF cases were managed conservatively, compared to 54% in salvage laryngectomy cases.The average hospitalization time for PCF patients was significantly longer at 35.6 days, compared to 12 days for non-PCF patients. Importantly, there were no fatal complications related to PCF in either group. Our study found that Pharyngocutaneous Fistula (PCF) occurs in both irradiated and non-irradiated patients, with T staging and pre-op albumin levels being significant risk factors. While PCF in non-irradiated patients can be treated conservatively, those in chemoradiation patients often require surgical intervention. Postoperative nutritional support like Feeding jejunostomy or Peg tube insertion aids in patient recovery from PCF.

The Value of Computed Tomography in Recurrent Laryngeal Cancer Following Organ Preservation Therapy.

This study aims to assess the accuracy of computed tomography (CT) in detecting recurrent laryngeal tumors after failed chemoradiation therapy (CRT). Local recurrence of laryngeal tumors following CRT has been reported in approximately 25%, yet it is often difficult to detect. Ten patients with laryngeal cancer who failed CRT and subsequently underwent salvage total laryngectomy were included. The laryngeal subsites involved in the tumor were identified based on postoperative pathology. The corresponding preoperative CT scans were selected for review by seven experts (head-and-neck surgeons or radiologists) who scored the extent of tumor spread on each scan on a 5-point scale, from no tumor detected to clearly visible tumor. The rates of high tumor detectability (scores 4-5) varied according to laryngeal subsite, from 75% in the glottic region, to 45% in the subglottic region, and to 19% in the supraglottic region (P=0.01). The detectability rates were higher on scans performed 2 years or more after CRT. The CT evaluation of laryngeal cancer after CRT has limited value, particularly in the epiglottis and subglottis.

Integrating novel immunotherapeutic approaches in organ-preserving therapies for bladder cancer.

Bladder cancer (BC) is a prevalent malignancy with significant morbidity and mortality. Over the years, the landscape of bladder cancer treatment has witnessed notable advancements, particularly in the realm of immunotherapy. Immunotherapy has emerged as a promising adjunct to organ-preserving approaches, harnessing the immune system's potential to target and eliminate cancer cells. Organ preservation strategies offer viable alternatives to radical cystectomy to avoid the morbidities associated with radical surgery, as well as to respond to the needs of patients unfit for or who have refused surgery. However, the challenge lies in achieving durable disease control while minimizing treatment-related toxicities. This review highlights the significance of immune checkpoint inhibitors, such as anti-programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) antibodies, in the treatment of localized bladder cancer. The clinical efficacy of immune checkpoint inhibitors, as both neoadjuvant and adjuvant therapies in combination with radiation or chemotherapy, is discussed. Moreover, the potential of immunotherapies beyond immune checkpoint inhibition, including combinations with bacillus Calmette-Guérin (BCG) instillations and/or investigational gene therapies, is explored. Furthermore, the predictive value of the tumour immune microenvironment for the success of these strategies is examined. Understanding the complex interplay between tumour immunity and therapeutic interventions can aid in identifying predictive biomarkers and tailoring personalized treatment strategies. Further research and clinical trials are warranted to optimize the use of immunotherapy in conjunction with organ-preserving therapies, potentially leading to enhanced patient outcomes and quality of life.

Novel image-guided marker aimed at organ-preserving therapies for prostate cancer.

We developed fiducial imaging-guidance markers for the prostate with less imaging artifacts than currently commercially available markers. The aim of this study was to evaluate the imaging artifacts and potential usefulness and safety of these novel fiducial imaging markers in preclinical experiments. We selected specific metal materials and a shape that can minimize artifacts in line with a license we obtained for a metal with a gold-platinum (Au-Pt) alloy composition that maximized artifact-free MRI images. Both phantom and canine prostate tests were conducted in order to evaluate the imaging artifacts for three imaging modalities, MRI, CT and ultrasound, and the risk of migration of the markers from the site of insertion to elsewhere, as well as crushing. The newly developed Au-Pt material had less imaging artifacts in the MRI, CT and ultrasound imaging modalities in comparison with current commercially available fiducial markers made from gold materials only. The Au-Pt markers had sufficient strength and durability and were considered to be potentially clinically useful and safe markers. The developed Au-Pt markers could be potential tools for accurate lesion-targeted, organ-preserving therapies such as lesion-targeted focal therapy and active surveillance in addition to conventional radiation therapies.

Radiotherapy combined with deep regional hyperthermia in elderly and frail patients with muscle-invasive bladder cancer: quality analysis of hyperthermia and impact on clinical results

Purpose: Radiotherapy (RT) in combination with deep regional hyperthermia (HT) after transurethral removal of bladder tumor (TURBT) can be offered to elderly and frail patients with muscle-invasive bladder cancer (MIBC). Methods: In total, 21 patients (mean age 84 years) with unifocal or multifocal MIBC received radiation to a dose of 48–50 Gy/16–20 fractions with weekly HT. The primary endpoint was the variation in temperature metrics, thermal dose expressed as cumulative equivalent minutes at 43 °C when the measured temperature is T90 (CEM43T90) and net power applied in target volume per each HT session. Secondary endpoints were three-year overall survival (OS), disease-free survival (DFS), local progression-free survival (LPFS) and toxicity. Results: The temperature metrics, CEM43T90, mean and maximum net power applied did not differ significantly among the HT sessions of the 21 patients. With a median follow-up of 65 months, 52% (95% CI 32–72%) of patients had died 3 years after treatment. The three-year DFS and LPFS rates were 62% (95%CI 41–79%) and 81% (95%CI 60–92%), respectively. The three-year bladder preservation rate was 100%. Three out of four patients with local failure received a thermal dose CEM43T90 below a median of 2.4 min. The rates of acute and late grade-3 toxicities were 10% and 14%, respectively. Conclusion: The reproducibility of HT parameters between sessions was high. A moderately high CEM43T90 (> 2.4 min) for each HT session seems to be preferable for local control. RT combined with HT is a promising organ-preservation therapy for elderly and frail MIBC patients.

Ultrasound imaging of the testes in children and adolescents

Ultrasound, the imaging method of choice to evaluate abnormalities of the testes and the scrotum, provides accurate anatomic details and allows the assessment of perfusion using color Doppler and power Doppler. Ultrasound represents arapid and reliable procedure which in most cases leads to aconclusive diagnosis. The three most common conditions in the clinical picture of acute scrotum are testicular torsion, torsion of the testicular appendages and inflammatory changes of the testis and the epididymis (epididymo-orchitis). Especially in the case of testicular torsion, rapid diagnosis is essential since time is an important factor to initiate organ-preserving therapy. High-frequency linear array transducer (at least 10 MHz), which allows detection of slow flow rates, is recommended.

Our Experience with Hydrogel-Coated Trisacryl Microspheres in Uterine Artery Embolization for the Treatment of Symptomatic Uterine Fibroids and Adenomyosis: A Follow-Up of 11 Years.

Uterine artery embolization (UAE) for the treatment of symptomatic uterine fibroids and non-controllable adenomyosis symptoms is a relatively new procedure for organ-preserving therapy. These benign conditions can become symptomatic in about 30% of women between the ages of 35 and 50. The purpose of the UAE either for fibroids or adenomyosis is the elimination of blood loss, the reduction in pain, and bulky or rectal pressure symptoms. The purpose of this study is to present our experience in UAE with the use of hydrogel-coated tris acryl microspheres for the treatment of symptomatic uterine fibroids and adenomyosis.

Are there any volume-related effects on treatment options for patients with penile cancer? Results of a survey among university hospitals in Germany and Austria

Currently, 959 men in Germany and 67 in Austria are diagnosed with penile cancer each year, with an increase of approximately 20% in the last decade [RKI 2021, Statcube.at 2023]. Despite the rising incidence, the number of cases per hospital remains low. The median annual number of penile cancer cases at university hospitals in the DACH region was 7 patients (IQR 5-10) in 2017 [E-PROPS group 2021]. The compromised institutional expertise due to low case numbers is compounded with inadequate adherence to penile cancer guidelines, as shown in several studies. The centralization, which is rigorously implemented in countries such as the UK, enabled a significant increase in organ-preserving primary tumor surgery and stage-adapted lymphadenectomies, as well as improved patient survival in cases of penile cancer, resulting in a claim for a similar centralization in Germany and Austria. The aim of this study was to determine the current effects of case volume on penile cancer related treatment options at university hospitals in Germany and Austria. In January 2023, a survey was sent to the heads of 48 urological university hospitals in Germany and Austria, including questions regarding case volume in 2021 (total number of inpatient and penile cancer cases), treatment options for primary tumors and inguinal lymphadenectomy (ILAE), the availability of a designated penile cancer surgeon, and the professional responsibility for systemic therapies in penile cancer. Correlations and differences related to case volume were statistically analyzed without adjustments. The response rate was 75% (n=36/48). In total, 626 penile cancer patients were treated at the 36 responding university hospitals in 2021, representing approximately 60% of the expected incidence in Germany and Austria. The annual median total number of cases was 2807 (IQR 1937-3653), and for penile cancer, it was 13 (IQR 9-26). There was no significant correlation between the total inpatient and penile cancer caseloads (p=0.34). The number of organ-preserving therapy procedures for the primary tumor, the availability of modern ILAE procedures, the presence of a designated penile cancer surgeon, and the responsibility for systemic therapies were not significantly influenced by the total inpatient or penile cancer case volume of the treating hospitals, regardless of whether the case volumes were dichotomized at the median or upper quartile. No significant differences between Germany and Austria were observed. Despite a significant increase in the annual number of penile cancer cases at university hospitals in Germany and Austria compared to 2017, we found no case volume-related effects on structural quality with respect to penile cancer therapy. In the light of the proven benefits of centralization, we interpret this result as an argument for the necessity of establishing nationally organized penile cancer centers with even higher case volumes compared to the status quo, in light of the proven benefits of centralization.

Survival in an era of organ preservation: an update on laryngeal cancer in Ireland

BackgroundLaryngeal cancer epidemiology has changed in recent years, with falling incidence observed internationally. Organ preservation therapies have revolutionised management, though some patients may be unsuitable and survival was noted to fall in the 2000s. This study examines trends in laryngeal cancer in Ireland.MethodsA retrospective cohort study of National Cancer Registry of Ireland data from 1994 to 2014.ResultsFrom a cohort of 2651, glottic disease was most common (62%, n = 1646). Incidence rose to 3.43 cases/100,000/year for 2010–2014. 5-year disease-specific survival (DSS) was 60.6% and did not change significantly over time. Overall survival (OS) for T3 disease managed with primary radiotherapy was similar to primary surgery (HR 0.98, p = 0.9). DSS for T3 disease improved with primary radiotherapy (HR 0.72, p = 0.045).ConclusionIncidence of laryngeal cancer in Ireland rose despite international trends, while survival changed little. Radiotherapy improves DSS for T3 disease but does not improve OS, possibly secondary to poor organ function post-radiotherapy.

Organ preservation and total neoadjuvant therapy for rectal cancer: Investigating long course chemoradiation versus short course radiation therapy.

3617 Background: The efficacy of long course chemoradiation (LCRT) vs. short course radiation therapy (SCRT) relative to organ preservation (OP) in rectal cancer (RC) is unknown. We compared OP rates between SCRT and LCRT total neoadjuvant therapy (TNT) strategies. Methods: During the COVID-19 pandemic we established an institutional SCRT mandate with no exceptions. For comparison, we identified RC patients treated with LCRT immediately before and after the mandate period. After completion of TNT, patients were restaged by clinical exam, endoscopy, and MRI. A watch and wait (WW) approach was recommended for patients with a clinical complete response (cCR), defined by the MSK regression schema. Total mesorectal excision (TME) was recommended for non-cCR patients. OP was defined as remaining TME-free with no evidence of disease in the pelvis. We performed survival analysis for: local regrowth rate, OP, disease-free survival (DFS), and overall survival (OS). The validated low anterior resection syndrome (LARS) questionnaire (LARS-Q) was used to determine percentage of patients with major LARS. Results: We identified 332 consecutive patients with non-metastatic rectal adenocarcinoma treated with TNT (Jan. 2018-Jan. 2021). Patient and tumor characteristics were similar in the LCRT (n = 256) and SCRT (n = 76) cohorts. No significant differences in high-risk features were noted. Most patients had clinical stage III disease (82% in LCRT vs. 83% in SCRT). Induction chemotherapy followed by consolidative radiation was the most common treatment order (78% (LCRT) vs. 70% (SCRT)). The median interval from end of TNT to clinical restaging was 8 weeks (LCRT) and 9 weeks (SCRT). The cCR rate was 46% in both cohorts. Among patients with a cCR, the likelihood of WW management was similar (98% (LCRT) vs. 94% (SCRT)). From start of TNT, the median follow-up was 32 and 28 months respectively for LCRT and SCRT. The 2-year OS (95% vs. 92%), DFS (78% vs 70%), and distant recurrence (20% vs. 21%) rates were similar. Among all patients, the 2-year OP rate was 40% (95% CI 35-47%) for LCRT and 29% (95% CI 20-42%) with SCRT. In those patients managed by WW, the 2-year local regrowth rate was 20% (95% CI 12-27%) with LCRT vs. 36% (95% CI 16-52%) with SCRT. Percentage of patients reporting major LARS symptoms were similar among WW patients post TNT: baseline (23% (LCRT) vs. 18% (SCRT)), 6-months (41% (LCRT) vs. 42% (SCRT)), and 12-months (25% (LCRT) vs. 15% (SCRT)). Conclusions: In this nonrandomized comparison, while cCR rates were similar, we observed a numerically higher local regrowth rate with SCRT-TNT than with LCRT-TNT. Rate of major-LARS symptoms were similar with LCRT-TNT than with SCRT-TNT. The ongoing ACO/ARO/AIO-18.1 trial, hypothesizing that LCRT-TNT will increase OP rates relative to SCRT-TNT, will definitively address this question.

Differentiating bladder cancer (BLCA) tumor immune microenvironment (TME) profiles based on predicted intrinsic radiosensitivity (RS).

e16622 Background: Radiation is an essential part of organ preservation therapy for muscle-invasive BLCA patients. There is increasing interest in use of immunotherapy in this setting and defining biomarkers of RS and immunity will be crucial to guide patient selection. We investigated whether predicted RS of BLCA patients can differentiate TME profiles based on RNA-seq. Methods: Twenty genomically-verified BLCA cell lines were profiled with log(TPM+1) normalized RNA-seq counts. Colony forming assays (CFA) for each cell line were done in triplicate with RS indices measured via area-under-the-cell-survival curve (AUC) and surviving fraction (SF) at varying doses (0-8Gy). The RS signature (RSS) was derived in two steps. First, NMF-decomposition of the RNA-seq data was done via CoGAPS v.3.6 run at k = 13 gene sets for 10,000 iterations then gene sets significantly correlated (p ≤ 0.05) with RS indices defined as an absolute Spearman’s rho >0.3 in at least 4/5 indices between AUC, SF2, SF4, SF6, and SF8 were combined. Secondly, the top 100-genes overexpressed by top-third most sensitive cell lines were identified by ComparativeMarkerSelection. The RSS contained genes shared between approaches and the RS-scores for the 408-patient TCGA-BLCA cohort were defined by averaging z-score normalized gene expression in the RSS. Patients were grouped as RS-high (top-quartile RS scores) and -low (bottom-quartile RS scores. Enrichment of the TME was assessed via EcoTyper algorithm and significant differences were defined a priori as: 1) Student’s t-test p ≤ 0.1 with Benjamini-Hochberg correction with an FDR of 0.2; 2) absolute correlation of r ≥ 0.4 between cell-state and RS-score; 3) ≥30% difference in enrichment between RS-high and RS-low. Results: Satisfactory CFA were obtained for 18 cell lines (range of RS indices: AUC = 3.40-5.94; SF2 = 0.32-0.75; SF4 = 0.09-0.42; SF6 = 0.02-0.19; SF8 = 0.002-0.09). CoGAPS analysis revealed 4 gene sets that were significantly correlated with RS totaling 1,997 genes. The RSS ultimately contained 78 genes and TCGA-BLCA RS scores ranged from -0.3 to 5.2. RS-high patients had significant enrichment for polymorphonuclear neutrophils (PMNs S02 state; 46-fold) and mast cells (S01 state; 77-fold). RS-low patients had significant enrichment for multiple cell-states including exhausted CD4 T-cells (S01 state; 1.31-fold; associated with CXCR6 & CTLA-4) and cancer-associated fibroblasts (S03 state, 1.33-fold; associated with POSTN & COL10A1). Conclusions: We demonstrate that predicted RS of BLCA patients is associated with a differential TME profile characterized by PMN inflammation and CD4 T-cell mediated immunosuppression among other cellular states. This potential link between RS and immunity may have broader implications for biomarker-guided immunotherapy as part of organ-preservation for BLCA patients although further validation is needed.

Uterine fibroids: modern methods of treatment, advantages and complications

The state of the reproductive system by women with uterine fibroids is considered as a part of this literature review. The main clinical manifestations of myomatous nodes were identified by writing the review: abnormal uterine and heavy menstrual bleeding, infertility, miscarriage, chronic pelvic pain, dysfunction of adjacent organs, which are indications for surgical treatment. It is noted that approximately 30 % of women with uterine fibroids suffer from abnormal uterine bleeding, leading to anemia and reduced quality of life. Chronic pelvic pain significantly reduces the quality of life of patients, worsening their functional and mental state and disrupting sexual function. This review focuses on reproductive problems in women with leiomyoma. Taking into consideration the high prevalence of this nosology and the need to preserve the fertility of patients, the review describes modern methods of treating patients with uterine myoma, including drug therapy surgical treatment and alternative methods. Currently, in order to stop the symptoms of uterine fibroids, as well as for preoperative preparation, conservative therapy is used, which allows to reduce pain, restore hemoglobin levels, reduce intraoperative blood loss and reduce surgery time. Reproductive disorders associated with uterine fibroids, such as infertility, recurrent miscarriage, and adverse obstetric outcomes, are a significant reason to improve organ-preserving therapies or develop new ones. Although hysterectomy is a radical treatment for uterine fibroids, it is unacceptable for patients who have not realized their reproductive function. Therefore, the most justified intervention is myomectomy with various surgical approaches, and as an alternative treatment, uterine artery embolization, radiofrequency ablation or high-intensity focused ultrasound treatment of uterine fibroids. These data allow us to conclude that the high prevalence and versatility of symptoms of uterine fibroids among patients of reproductive age determine the relevance of searching for optimal methods of treatment.

Organ preservation and total neoadjuvant therapy for rectal cancer: Investigating long-course chemoradiation versus short-course radiation therapy.

10 Background: Interest in organ preservation (OP) strategies for rectal cancer (RC) patients persists. The efficacy of long course chemoradiation (LCRT) vs. short course radiation therapy (SCRT) relative to OP is unknown. We compared OP rates between SCRT and LCRT total neoadjuvant therapy (TNT) strategies. Methods: During the COVID-19 pandemic we established an institutional SCRT mandate with no exceptions. For comparison, we identified RC patients treated with LCRT immediately before and after the mandate period. After completion of TNT, patients were restaged by clinical exam, endoscopy, and MRI. A watch and wait (WW) approach was recommended for patients with a clinical complete response (cCR), defined by the MSK regression schema. Total mesorectal excision (TME) was recommended for non-cCR patients. OP was defined as alive, TME-free, and with no evidence of disease in the pelvis. We performed survival analysis for: local regrowth rate, OP, disease-free survival (DFS), and overall survival (OS). Results: We identified 563 consecutive patients with RC treated with TNT, of whom 231 were excluded due to either metastatic disease, synchronous/metachronous malignancies, or non-adenocarcinoma histology (Jan. 2018-Jan. 2021). Patient and tumor characteristics were similar in the LCRT (n = 256) and SCRT (n = 76) cohorts. No significant differences in high-risk features were noted. Most patients had clinical stage III disease (82% in LCRT vs. 83% in SCRT). Induction chemotherapy followed by consolidative radiation was the most common treatment order (78% (LCRT) vs. 70% (SCRT)). The median interval from end of TNT to clinical restaging was 8 weeks (LCRT) and 9 weeks (SCRT). The cCR rate was 46% in both cohorts. The cCR rate was numerically higher in patients treated with radiation first, as compared to chemotherapy first (53% vs. 44% (LCRT) and 52% vs. 43% (SCRT)). Among patients with a cCR, the likelihood of WW management was similar (98% (LCRT) vs. 94% (SCRT)). From start of TNT, the median follow-up was 32 and 28 months respectively for LCRT and SCRT. The 2-year OS (95% vs. 92%), DFS (78% vs 70%), and distant recurrence (20% vs. 21%) rates were similar. Among all patients, the 2-year OP rate was 40% (95% CI 35-47%) for LCRT and 29% (95% CI 20-42%) with SCRT. In those patients managed by WW, the 2-year local regrowth rate was 20% (95% CI 12-27%) with LCRT vs. 36% (95% CI 16-52%) with SCRT. Conclusions: In this nonrandomized comparison, while cCR rates were similar, we observed a numerically higher OP rate with LCRT-TNT than with SCRT-TNT. The ongoing ACO/ARO/AIO-18.1 trial, hypothesizing that LCRT-TNT will increase OP rates relative to SCRT-TNT, should definitively answer this question.

Quality-of-life outcomes in older patients with early-stage rectal cancer receiving organ-preserving treatment with hypofractionated short-course radiotherapy followed by transanal endoscopic microsurgery (TREC): non-randomised registry of patients unsuitable for total mesorectal excision

Older patients with early-stage rectal cancer are under-represented in clinical trials and, therefore, little high-quality data are available to guide treatment in this patient population. The TREC trial was a randomised, open-label feasibility study conducted at 21 centres across the UK that compared organ preservation through short-course radiotherapy (SCRT; 25 Gy in five fractions) plus transanal endoscopic microsurgery (TEM) with standard total mesorectal excision in adults with stage T1-2 rectal adenocarcinoma (maximum diameter ≤30 mm) and no lymph node involvement or metastasis. TREC incorporated a non-randomised registry offering organ preservation to patients who were considered unsuitable for total mesorectal excision by the local colorectal cancer multidisciplinary team. Organ preservation was achieved in 56 (92%) of 61 non-randomised registry patients with local recurrence-free survival of 91% (95% CI 84-99) at 3 years. Here, we report acute and long-term patient-reported outcomes from this non-randomised registry group. Patients considered by the local colorectal cancer multidisciplinary team to be at high risk of complications from total mesorectal excision on the basis of frailty, comorbidities, and older age were included in a non-randomised registry to receive organ-preserving treatment. These patients were invited to complete questionnaires on patient-reported outcomes (the European Organisation for Research and Treatment of Cancer Quality of Life [EORTC-QLQ] questionnaire core module [QLQ-C30] and colorectal cancer module [QLQ-CR29], the Colorectal Functional Outcome [COREFO] questionnaire, and EuroQol-5 Dimensions-3 Level [EQ-5D-3L]) at baseline and at months 3, 6, 12, 24, and 36 postoperatively. To aid interpretation, data from patients in the non-randomised registry were compared with data from those patients in the TREC trial who had been randomly assigned to organ-preserving therapy, and an additional reference cohort of aged-matched controls from the UK general population. This study is registered with the ISRCTN registry, ISRCTN14422743, and is closed. Between July 21, 2011, and July 15, 2015, 88 patients were enrolled onto the TREC study to undergo organ preservation, of whom 27 (31%) were randomly allocated to organ-preserving therapy and 61 (69%) were added to the non-randomised registry for organ-preserving therapy. Non-randomised patients were older than randomised patients (median age 74 years [IQR 67-80] vs 65 years [61-71]). Organ-preserving treatment was well tolerated among patients in the non-randomised registry, with mild worsening of fatigue; quality of life; physical, social, and role functioning; and bowel function 3 months postoperatively compared with baseline values. By 6-12 months, most scores had returned to baseline values, and were indistinguishable from data from the reference cohort. Only mild symptoms of faecal incontinence and urgency, equivalent to less than one episode per week, persisted at 36 months among patients in both groups. The SCRT and TEM organ-preservation approach was well tolerated in older and frailer patients, showed good rates of organ preservation, and was associated with low rates of acute and long-term toxicity, with minimal effects on quality of life and functional status. Our findings support the adoption of this approach for patients considered to be at high risk from radical surgery. Cancer Research UK.

Nasal Cavity Squamous Cell Carcinoma: Factors Associated With Treatment Outcomes and Potential Organ Preservation.

Squamous cell carcinoma of the nasal cavity (NCSCC) is a rare, challenging malignancy. Surgical resection of this tumor can cause significant facial deformity, and indications for adjuvant or organ preservation therapies are not well-described. To examine the impact of treatment regimen on survival outcomes in NCSCC and to compare surgical to non-surgical based therapies. The National Cancer Database was queried for NCSCC from 2004 to 2014. Patient demographics, tumor characteristics, and treatment regimen were compared for the entire cohort. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen and surgical margins on overall survival (OS) for early and late-stage disease. A total of 1883 NCSCC patients were identified. The OS for the cohort was 83 months, and median age at diagnosis was 65 years. NCSCC patients who underwent surgery followed by adjuvant radiation therapy (RT) had a better OS compared to definitive RT (HR: 0.58, P < .001). In early stage NCSCC (T1/T2, N0), there was no significant difference in OS between patients treated with surgery only or surgery with adjuvant RT compared to definitive RT. In advanced stage NCSCC, surgery with adjuvant RT had a better OS compared to definitive chemoradiation. Having positive margins was shown to predict a worse OS when compared to negative margins in surgical patients despite adjuvant RT or chemoradiation. NCSCC appears to be best treated with surgery followed by adjuvant RT in advanced-stage disease whereas in early-stage disease, surgery does not improve OS compared to definitive RT.

S3745 An Uncommon Case of Helicobacter pylori-Negative Gastric MALT Lymphoma

Introduction: Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is a type of non-Hodgkin's lymphoma with concomitant H. pylori infection. Approximately 5-10% of patients are not. Recent studies on H. pylori-negative gastric MALT lymphomas have suggested that H. pylori eradication therapy is effective in a proportion of patients with this disease and could even be considered a first-line treatment. Here, we present this uncommon and unique case. Case Description/Methods: A 58-year-old man, with PMH of prostate cancer and DVT not on anticoagulation, was initially admitted for seizures and altered mental status under the impression of bacterial meningitis. He had an upper GI bleed during the same hospitalization, and an inpatient upper endoscopy showed a Forrest 1a ulcer in the gastric fundus s/p clipping (Fig 1A). A repeat upper endoscopy three months later showed gastric erythema and a 6 mm non-bleeding healing gastric ulcer in the fundus (Fig 1B). The pathology report of antrum biopsy showed fundic and transitional zone gastric mucosa, mild chronic gastritis without intestinal metaplasia or dysplasia, and the presence of a few atypical lymphocytes. The body biopsy showed fundic/body type gastric mucosa, and findings were compatible with low-grade B-cell lymphoma, favoring extranodal marginal zone lymphoma of MALT lymphoma (Fig 1C). The patient was empirically treated for H. pylori with Bismuth-based quadruple therapy. The patient improved on follow-up with GI. Hematology-Oncology is currently planning for FISH for t(11;18) and/or MYD88 mutation status to assist in the differential, as the H. pylori strain was negative on biopsy. Discussion: Several theories describe pathways for lymphoid proliferation in H. pylori-negative patients, but the exact mechanism has yet to be determined. Currently, it is deemed multifactorial. There is a high incidence of translocation (11;18)(q21;q21) in H. pylori-negative MALT lymphomas is seen. Using radiation therapy for patients with early-stage (Lugano I/II) gastric MALT lymphomas that are negative for H. pylori infection is recommended, with clinical remission rates of up to 100%. Conversely, organ-preserving therapy has no added benefit and surgical treatment is rarely pursued. Therefore, it is recommended to eliminate the presence of H. pylori and evaluate for this translocation. Recent studies have suggested that H. pylori eradication therapy is effective in some proportion of these patients and could be considered a first-line treatment.Figure 1.: A) Upper endoscopy image of Forrest Class 1a ulcer s/p two clips. There is a spurting gastric ulcer with spurting hemorrhage. B) Upper endoscopy of gastric erythema and a 6 mm non-bleeding healing gastric ulcer in the fundus. C) Pathology: Low power view, H&E stain, of antrum biopsy showing fundic and transitional zone gastric mucosa, mild chronic gastritis without intestinal metaplasia or dysplasia, and the presence of a few atypical lymphocytes Immunohistochemistry studies showed atypical lymphocytes CD20+, CD79a+, PAX5+, CD5-, CD10-, BCL6-, BCL2+, CD43+, CyclinD1-, BCL6, and CD10, highlighting very small, scattered, disrupted germinal centers. CD3 and CD5 highlighted numerous admixed T-cells. Ki-67 was overall low (5-10%). Kappa(ish) and Lambda(ish) stains showed that the plasma cells were kappa-restricted, and had low mitotic activity, supporting the diagnosis of marginal zone lymphoma.

A rare case of endometritis after caesarean section. Case report

The article describes a rare case of endometritis after abdominal delivery. Attention is drawn to the possibility of developing ischemia and necrosis of the uterine tissue when using the Reverden suture, as well as the development of a significant local inflammatory response due to the individual reaction to the suture material used. A case of non-surgical integrated approach to the treatment of endometritis with local tissue rejection is presented. A positive outcome of organ-preserving therapy of endometritis in terms of ischemic and necrotic changes in the area of the postoperative suture on the uterus was shown. Conservative therapy included the use of a beta-lactam class carbapenem and an antimicrobial peptide complex.

STAR-TREC phase II: Can we save the rectum by watchful waiting or transanal surgery following (chemo)radiotherapy versus total mesorectal excision for early rectal cancer?

3502 Background: No randomised trials have compared non-operative organ preservation (OP) therapy for early-stage rectal cancer versus standard of care (SoC) using total mesorectal excision (TME) alone. STAR-TREC evaluated the feasibility of recruiting to a study comparing contrasting OP therapies, optimised for treatment of early tumours, versus SoC. Methods: STAR-TREC was a prospective, randomised, open-label, feasibility study in the UK, Netherlands and Denmark. Patients with biopsy proven adenocarcinoma of the rectum, staged ≤mrT3b N0 M0, ≤40mm diameter, ECOG 0-1 were randomised in a 1:1:1 ratio to TME, OP via mesorectal short-course radiotherapy (5x5 Gy), or OP via mesorectal chemo-radiotherapy (25x2 Gy + capecitabine) (Peters FP et al. Mesorectal radiotherapy for early stage rectal cancer: A novel target volume. Clin Transl Radiat Oncol 2020; 21: 104-11). Standardised response assessment classified OP cases as complete response for no further treatment, partial response for transanal endoscopic microsurgery or poor response for TME by 20 weeks. Surveillance following OP consisted of 3-monthly endoscopy/MRI. All cases had CT thorax/abdomen/pelvis at 24 months (m). The primary outcome was recruitment rate over 2 years, with randomisation of 120 international cases calculated as sufficient to support a phase III trial. Secondary outcomes included acute toxicity, stoma and OP rates at 12m, disease free survival (DFS) and non-regrowth DFS (NRDFS) at 24m and EORTC QLQ-C30 summary score at 12 and 24m. Phase II analysis was pre-specified, approved by the data monitoring committee conditional upon grouping of OP arms to inform phase III design, without prejudicing the outcome (STAR-TREC Phase III protocol. Colorectal Disease 2022). Results: Recruitment endpoints were met on 28 Oct 2019. Key secondary outcomes are tabulated by intention to treat. No 6-month mortality occurred. Conclusions: OP pathways optimised for early tumours reduce acute surgical morbidity without introducing substantial radiation toxicity to achieve OP in 60% with no increase in NRDFS at 24m compared to SoC. Overall quality of life was evenly matched. STAR-TREC phase III will determine the optimal strategy for achieving OP (STAR-TREC Phase III protocol. Colorectal Disease 2022). Clinical trial information: NCT02945566. [Table: see text]

Carbon Ion Beam Boost Irradiation in Malignant Tumors of the Nasal Vestibule and the Anterior Nasal Cavity as an Organ-Preserving Therapy.

BackgroundSurgery and radiotherapy are current therapeutic options for malignant tumors involving the nasal vestibule. Depending on the location, organ-preserving resection is not always possible, even for small tumors. Definitive radiotherapy is an alternative as an organ-preserving procedure. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of the current study was to analyze toxicity, local control (LC), and organ preserving survival (OPS) after irradiation of carcinoma of the nasal vestibule with raster-scanned carbon ion radiotherapy boost (CIRT-B) combined with volumetric intensity modulated arc therapy (VMAT) with photons.MethodsBetween 12/2015 and 05/2021, 21 patients with malignant tumors involving the nasal vestibule were irradiated with CIRT-B combined with VMAT and retrospectively analyzed. Diagnosis was based on histologic findings. A total of 17 patients had squamous cell carcinoma (SCC) and 4 had other histologies. In this series, 10%, 67%, and 24% of patients had Wang stages 1, 2, and 3 tumors, respectively. Three patients had pathologic cervical nodes on MRI. The median CIRT-B dose was 24 Gy(RBE), while the median VMAT dose was 50 Gy. All patients with pathologic cervical nodes received simultaneously integrated boost with photons (SIB) up to a median dose of 62.5 Gy to the pathological lymph nodes. Eight patients received cisplatin chemotherapy. All patients received regular follow-up imaging after irradiation. Kaplan–Meier estimation was used for statistical assessment.ResultsThe median follow-up after irradiation was 18.9 months. There were no common toxicity criteria grade 5 or 4 adverse events. A total of 20 patients showed grade 3 adverse events mainly on skin and mucosa. All patients were alive at the end of follow-up. The median OPS after treatment was 56.5 months. The 6- and 24-month OPS were 100% and 83.3%, respectively. All local recurrences occurred within 12 months after radiotherapy. The median progression free survival (PFS) after treatment was 52.4 months. The 6-, 12-, and 24-month PFS rates were 95%, 83.6%, and 74.3%, respectively.ConclusionCIRT-B combined with VMAT in malignant tumors of the nasal vestibule is safe and feasible, results in high local control rates, and thus is a good option as organ-preserving therapy. No radiation-associated grade 4 or 5 acute or late AE was documented.