Palliative Cancer Treatment Research Articles

Estimation in discrete time coarsened multivariate longitudinal models.

We consider the analysis of longitudinal data of multiple types of events where some of the events are observed on a coarser level (e.g. grouped) at some time points during the follow-up, for example, when certain events, such as disease progression, are only observable during parts of follow-up for some subjects, causing gaps in the data, or when the time of death is observed but the cause of death is unknown. In this case, there is missing data in key characteristics of the event history such as onset, time in state, and number of events. We derive the likelihood function, score and observed information under independent and non-informative coarsening, and conduct a simulation study where we compare bias, empirical standard errors, and confidence interval coverage of estimators based on direct maximum likelihood, Monte Carlo Expectation Maximisation, ignoring the coarsening thus acting as if no event occurred, and artificial right censoring at the first time of coarsening. Longitudinal data on drug prescriptions and survival in men receiving palliative treatment for prostate cancer is used to estimate the parameters of one of the data-generating models. We demonstrate that the performance depends on several factors, including sample size and type of coarsening.

A Review on Therapeutic Potential of Cold Atmospheric Plasma Therapy in Oral Cancer: Emerging Trends and Amelioration

Oral Squamous Cell Carcinoma (OSCC) is a life-threatening disease. Many patients are in advanced stages at the time of diagnosis, resulting in high mortality and morbidity and clinical problems that make clinical management challenging. Due to advancements in early diagnostic procedures of cancer and its treatment, the number of patients suffering from OSCC has decreased. Still, the number of death due to cancer has not been reduced. In many circumstances, chemotherapy has major side-effects. Cold Atmospheric pressure Plasma (CAP) is a new therapy option that seems to be used mostly as part of a palliative cancer treatment program to provide comfort to these patients. Using a gas that is ionised partially, known as CAP therapy, researchers are now able to treat cancer. The identification of the anticancer properties of CAP, and clinical efficacy, can open up the door for the development of a wide range of synergistic and individualised plasma-enabled therapies. These drugs can potentially enhance current therapies in the direction of safer, more efficient treatment modalities and provide a gentle but efficacious cancer singleagent therapy with a wide therapeutic window and good selectivity.

The Power Setting of Focused Ultrasound for the Palliative Treatment of Advanced Pancreatic Cancer: A Study in an Ex Vivo Bovine Liver

High-intensity focused ultrasound (HIFU) ablation has been widely used in advanced pancreatic cancer in recent years. In numerous studies, HIFU has been shown to be safe, effective, and practicable, but there are a few HIFU-related adverse effects. The patients’ discomfort during therapy increased proportionally with increasing delivered energy and pain levels seemed to be independent of the dose of anesthetic or sedation. If the power used in therapy is too high, the temperature of the target area will rise rapidly, and the boiling and cavitation make the shape of the necrosis area difficult to control. In recent years, moderate-intensity focused ultrasound (MIFU) has also been shown to heat the tumor locally for palliative treatment. Choosing the appropriate power and effectively controlling the tissue temperature until reaching the threshold for thermal necrosis are of great significance for ensuring the safety of palliative treatment. In this study, an infrared temperature measurement experimental system was set up to measure the temperature rise at different power in an ex vivo bovine liver. It was found that when the acoustic intensity of the focused ultrasound was lower than the cavitation threshold (within the range of the MIFU), the temperature of the tissue kept rising at a steady rate and could still reach the thermal damage threshold temperature within tens of seconds. The results showed that the temperature induced by the MIFU was almost entirely dependent on the thermal effect, and the temperature of the tissue at the end of sonication was linearly related to the power. Finally, this study considered the effect of blood perfusion on the temperature for the application of focused ultrasound in the palliative treatment of advanced pancreatic cancer with the goal of providing a reference for the application of focused ultrasound in the palliative treatment of advanced pancreatic cancer.

HPB P37 Outcomes following EUS choledocho-duodenostomy for the palliative treatment of peri-ampullary cancer following unsuccessful ERCP – A single centre experience

Abstract Background EUS-guided choledocho-duodenostomy is an option to relieve jaundice after a failed ERCP, in patients with locally advanced or metastatic peri-ampullary cancers. We aim to assess the technical success, safety and outcomes of the procedure in our practice. Methods All consecutive adult patients that underwent EUS-guided CBD stent placement after a failed ERCP between December 2019 and May 2022 at the Queens Medical Centre, Nottingham were included. Studied variables included demographics, technical characteristics and outcomes including length of stay, normalisation of bilirubin level, complication rate and 30-day mortality rate. Results Twenty-six consecutive patients were included in this study (12 males, 14 females). The mean age was 75 (range 52–92) years. Pancreatic cancer was present in 15 patients (57.6%), 4 patients (15.3%) each had ampullary cancer and other malignant peri-ampullary lesions while 3 patients (11.5%) had duodenal cancer. Metastatic disease was present in 13 patients (50%). Mean ECOG status was 2 (n= 13). ERCP was unsuccessful due to an inability to cannulate the CBD (n= 3), duodenal tumour infiltration (n=10), destroyed ampulla (n=6) and inaccessible papilla (n=5). EUS-guided CBD stent placement was successful in 24 patients (92.3%). The mean CBD diameter at presentation was 19.5 mm (range 14–32) and mean distance between the bile duct and duodenum was 4.2 mm. The complication rate was 15.3% (4/26 patients). Complications included cholecystitis, stent blockage, slow bleeding and bowel perforation after a displaced stent. Median post-procedure LOS was 5.5 days. A reduction in bilirubin to <50% was observed in 19 patients (73%) by discharge. There were 2 biliary re-interventions in the group. The overall 30-day mortality rate was 38.4% (n=10) with a procedure specific mortality of 11.5% (n=3). Conclusions EUS-guided choledocho-duodenostomy is an effective and safe option to relieve jaundice in this group of patients.

What is confirmed in the treatment of colon cancer?

Colorectal cancer is the second most common cancer diagnosed in Germany and is the third most frequent cause of cancer-related death in both males and females. The majority of colorectal cancers occur via the adenoma-carcinoma sequence of origin. This means that colorectal cancers can be endoscopically detected in premalignant stages and can be curatively treated within the framework of early detection. Screening colonoscopy and, to a lesser extent, fecal occult blood testing, have led to areduction in the colon cancer-related incidence and mortality. The acceptance and the use of screening colonoscopy should therefore be developed further. Treatment strategies for colorectal cancer are based on TNM staging, supplemented by anatomical and histopathological risk features as well as individual patient characteristics and treatment preferences. The molecular tumor profile is increasingly used to complement decision-making in the surgical, adjuvant and palliative treatment of colorectal cancer. Colon and rectal cancer have many similarities; however, they differ in the preoperative, surgical and adjuvant treatment strategies. This article focuses on colon cancer.

The Photosensitizer Temoporfin (mTHPC) - Chemical, Pre-clinical and Clinical Developments in the Last Decade.

This review follows the research, development and clinical applications of the photosensitizer 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC, temoporfin) in photodynamic (cancer) therapy (PDT) and other medical applications. Temoporfin is the active substance in the medicinal product Foscan® authorized in the EU for the palliative treatment of head and neck cancer. Chemistry, biochemistry and pharmacology, as well as clinical and other applications of temoporfin are addressed, including the extensive work that has been done on formulation development including liposomal formulations. The literature has been covered from 2009 to early 2022, thereby connecting it to the previous extensive review on this photosensitizer published in this journal [Senge, M. O. and J. C. Brandt (2011) Photochem. Photobiol. 87, 1240-1296] which followed its way from initial development to approval and clinical application.

Palliative Treatment of Esophageal Cancer Using Calcium Electroporation.

Calcium electroporation (CaEP) is a novel cancer therapy wherein high intracellular calcium levels, facilitated by reversible electroporation, trigger tumor necrosis. This study aimed to establish safety with CaEP within esophageal cancer. Patients with non-curable esophageal cancer were included at Copenhagen University Hospital Rigshospitalet in 2021 and 2022. In an outpatient setting, calcium gluconate was injected intratumorally followed by reversible electroporation applied with an endoscopic electrode. The primary endpoint was the prevalence of adverse events, followed by palliation of dysphagia. All patients were evaluated with CT and upper endoscopies up to two months after treatment. The trial was registered at ClinicalTrials.gov (NCT04958044). Eight patients were treated. One serious adverse event (anemia, requiring a single blood transfusion) and three adverse events (mild retrosternal pain (two) and oral thrush (one)) were registered. Initially, six patients suffered from dysphagia: two reported dysphagia relief and four reported no change. From the imaging evaluation, one patient had a partial response, three patients had no response, and four patients had progression. Six months after treatment, the patient who responded well was still in good condition and without the need for further oncological treatment. CaEP was conducted in eight patients with only a few side effects. This study opens the way for larger studies evaluating tumor regression and symptom palliation.

Radiation Therapy for Bridging and Improving CAR-T Cell Therapy

<h3>Purpose/Objective(s)</h3> CD19-targeted chimeric antigen receptor (CAR) T cells have transformed the treatment of patients with relapsed or refractory CD19-positive hematologic malignancies. However, a significant subset of these patients either fails to respond or eventually relapses. Moreover, patients who are candidates for CART-19 therapy often have symptomatic disease that requires some form of treatment to support them during the manufacture period. An ideal bridging therapy would simultaneously both (1) sensitize the tumor to CART-19 attack to increase antitumor control and (2) debulk the disease during manufacture. Radiotherapy (RT) is an established curative and palliative cancer treatment regimen, with approximately half of cancer patients with solid tumors receiving RT sometime during their disease. Several reports have underscored the existence of threshold doses (and regimens) that are able to switch on different damage programs that profoundly affect responses to therapy by eliciting potent immune modulatory effects, prompting immunologically mediated tumor cell death. These effects have been attributed to multiple pathways, including the activation of the cGMP-cAMP Synthetase (cGAS), Stimulator of Interferon Genes (STING) pathway with Type I Interferons expression, and tumor associated antigen (TAA) cross priming with anti-tumor CD8⁺ T cell elicitation, ultimately inducing "abscopal" effects. By virtue of the immunomodulatory effects of RT, we hypothesize that RT could serve as a successful bridging strategy for CAR T-cell therapy. <h3>Materials/Methods</h3> To investigate this hypothesis, we established the A20 Lymphoma CART-19 therapy mouse model in our lab and used it to perform preliminaries experiments. A20 cells were implanted into both flanks of the animals. Mimicking human immune adjuvant doses used in our institute for RT bridging, 20 days after tumor cell implantation, we radiated one of the two tumors using a dose of 8Gy divided in two fractions of 4Gy each. Twenty-four hours later 1 × 10ep6 CART-19 cells were infused intravenously. <h3>Results</h3> While the effects of RT in combination with CART-19 have similar impact on the tumor growth of the irradiated mass, a significant increase of the antitumor effects of the single therapy was observed on the non-irradiated tumor. FACS studies demonstrated heavy leukocyte infiltration with increased presence of infused CART-19 as well indigenous T cells. To investigate possible molecular mechanisms involved in the increased effects on the non-irradiated tumor, we performed a qPCR array and observed increased expression of genes linked to cross priming, including IFN type I and Batf3. A20 cells express the ectopic retroviral antigen gp70 with well characterized AH1 immune-dominant epitope. AH1 tetramer staining on infiltrating T cells demonstrated increased staining in tumor from mice treated with the combination. <h3>Conclusion</h3> Overall these results suggest RT may serve as optimal debulking and bridging therapy for CAR-T cell therapy.

Guidelines and workflow for virtual simulation.

49 Background: An important component of radiation treatment planning is the CT simulation which involves several steps including patient positioning, imaging in the treatment position, and placement of an isocenter, a point through which the central rays of the radiation beams pass. As radiation therapy is an important component of palliative treatment for metastatic cancer, some patients require multiple courses which may be temporally proximate. This creates a burden for patients who may be challenged with regard to mobility, distance, and logistics coordinating travel to the department. We sought a clinical workflow that maintains the integrity of the simulation process but allows the potential use of previously obtained treatment planning imaging to create a new treatment plan (i.e. virtual CT simulation). We present our workflow and experience here. Methods: A multidisciplinary group developed a virtual simulation workflow and identified critical criteria to safely and reliably proceed with virtual simulation. These included: time from initial CT simulation (&lt; 14 days), adequacy of patient positioning and immobilization, as well as appropriate inclusion of the entire “virtual” planning treatment volume (PTV) and organs at risk (OARs) in the original scan. Specific virtual simulation care paths were created in treatment planning software (Aria®, Varian Medical Systems) for case tracking. A pilot was initiated to monitor the workflow for the first 10 patients and corrections to the workflow were made. Thereafter the program was randomly audited and the QA reporting system monitored for reported error events. Results: The virtual simulation workflow pilot was initiated in June 2020. Of the first 50 virtual simulation requests, 48 were approved (96%). Two cases were denied due to inadequate immobilization. There was only one event reported pertaining to set up uncertainty requiring clarification from physics. Conclusions: Given the success of the virtual simulation criteria and workflow we will continue this practice and will monitor the cases as well as RISQ events closely. Based on feedback we have received we will expand the window of time to request a virtual simulation from 14 days to 21 days after original simulation and will also allow for up to 3 virtual isocenters to be placed.

S2202 A Rare Case of Colonic Intussusception After Self Expandable Metal Stent Placement

Introduction: Endoscopically placed colonic stenting is a palliative measure that can be used for unresectable etastatic colon cancer. It is a relatively safe procedure with a low mortality rate of about 1%. Intussusception is a rare complication of colonic stenting that occurs when the bowel telescopes about itself, possibly leading to obstruction or ischemia. Here we present a patient with intussusception 6 days after placement of a self-expandable rectosigmoid metal stent. We demonstrate successful reduction of rectosigmoid intussusception through a colonoscopy with air insufflation. Case Description/Methods: A 35-year-old female presented with 3 days of constant and progressively-worsening rectal pain, bloody rectal discharge, and thin stool. Her past medical history was significant for metastatic colon cancer treated with sigmoid colectomy and chemotherapy 2 years prior, with recurrence of disease requiring palliative self-expandable rectosigmoid metal stent placement 6 days prior to arrival. Vital signs were normal. She did not appear in acute distress and was hemodynamically stable. Pertinent examination findings included lower abdominal tenderness, normal bowel sounds, and normal rectal tone. Labs revealed WBC 12.4, Hgb 13.2, Plt 443, AST 14, ALT 8, ALP 77, total bilirubin 0.7, and a lactate of 0.9. CT scan of the abdomen and pelvis revealed intussusception at the proximal sigmoid colon without evidence of bowel obstruction. Colonoscopy revealed ball-shaped mucosa with a dusky appearance at the proximal end of the stent, consistent with intussusception and ischemic colitis. The intussusception was successfully reduced with air insufflation through colonoscopy. The patient tolerated the procedure well and was started on a diet the next day with an improvement in her rectal pain and resolution of rectal discharge (Figure). Discussion: Endoscopic colonic stenting remains a valuable palliative treatment for metastatic colon cancer. Survival rates of metastatic colon cancer do not significantly differ between palliative colonic stenting and colonic resection. However, there are fewer complications with colonic stenting than colectomy, making palliative stenting a preferred option. Intussusception is a rare complication of colonic stenting that is often treated surgically in adults. Here we demonstrate successful reduction of intussusception through colonoscopic air insufflation. We hope to bring awareness of this complication and consideration to air insufflation as first-line therapy.Figure 1.: A. A view of the distal aspect of the rectosigmoid stent revealing adequate translocation of tumor mass without evidence of obstruction. B. A view of the proximal aspect of the rectosigmoid stent revealing a dusky appearance,with thickening of the bowel. C. A view of the proximal aspect of the stent with the ball-shaped mass in a dusky appearance consistent with intussusception, as seen by arrows.

Evaluation of biosimilar trastuzumab MYL-1401O in HER2-positive breast cancer.

The trastuzumab biosimilar MYL-1401O has demonstrated equivalent efficacy and comparable safety to reference trastuzumab (RTZ) in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) as HER2 monotherapy. Here, we present the first real-world comparison of MYL-1401O vs RTZ as single/dual HER2-targeted therapy for the neoadjuvant, adjuvant, and palliative treatment of HER2-positive breast cancer in the first and second lines. We retrospectively investigated medical records. We identified patients with HER2-positive early-stage breast cancer (EBC) (n = 159) who had received neoadjuvant chemotherapy with RTZ or MYL-1401O ± pertuzumab (n = 92) or adjuvant chemotherapy with RTZ or MYL-1401O plus taxane (n = 67) between January 2018 and June 2021, as well as patients with MBC (n = 53) who had received palliative first-line treatment with RTZ or MYL-1401O and docetaxel ± pertuzumab or second-line treatment with RTZ or MYL-1401O and taxane between January 2018 and June 2021. The rate of achieving pathologic complete response in patients receiving neoadjuvant chemotherapy was similar between those receiving MYL-1401O and RTZ (62.7% [37/59] and 55.9% [19/34], respectively; P = .509). Progression-free survival (PFS) at 12, 24, and 36 months was similar in the 2 cohorts of the EBC-adjuvant group: 96.3%, 84.7%, and 71.5%, respectively, in patients receiving MYL-1401O, and 100%, 88.5%, and 64.8% in patients receiving RTZ (P = .577). Median PFS was also similar in MBC, at 23.0 months (95% CI, 9.8-26.1) in patients receiving MYL-1401O and 23.0 months (95% CI, 19.9-26.0) in patients receiving RTZ (P = .270). The overall response rate, disease control rate, and cardiac safety profiles did not show significant differences in efficacy outcomes between the 2 groups. These data suggest that biosimilar trastuzumab MYL-1401O has similar effectiveness and cardiac safety to RTZ in patients with HER2-positive EBC or MBC.

Design of a multinational randomized controlled trial to assess the effects of structured and individualized exercise in patients with metastatic breast cancer on fatigue and quality of life: the EFFECT study

BackgroundMany patients with metastatic breast cancer experience cancer- and treatment-related side effects that impair activities of daily living and negatively affect the quality of life. There is a need for interventions that improve quality of life by alleviating fatigue and other side effects during palliative cancer treatment. Beneficial effects of exercise have been observed in the curative setting, but, to date, comparable evidence in patients with metastatic breast cancer is lacking. The aim of this study is to assess the effects of a structured and individualized 9-month exercise intervention in patients with metastatic breast cancer on quality of life, fatigue, and other cancer- and treatment-related side effects.MethodsThe EFFECT study is a multinational, randomized controlled trial including 350 patients with metastatic breast cancer. Participants are randomly allocated (1:1) to an exercise or control group. The exercise group participates in a 9-month multimodal exercise program, starting with a 6-month period where participants exercise twice a week under the supervision of an exercise professional. After completing this 6-month period, one supervised session is replaced by one unsupervised session for 3 months. In addition, participants are instructed to be physically active for ≥30 min/day on all remaining days of the week, while being supported by an activity tracker and exercise app. Participants allocated to the control group receive standard medical care, general written physical activity advice, and an activity tracker, but no structured exercise program. The primary outcomes are quality of life (EORTC QLQ-C30, summary score) and fatigue (EORTC QLQ-FA12), assessed at baseline, 3, 6 (primary endpoint), and 9 months post-baseline. Secondary outcomes include physical fitness, physical performance, physical activity, anxiety, depression, pain, sleep problems, anthropometric data, body composition, and blood markers. Exploratory outcomes include quality of working life, muscle thickness, urinary incontinence, disease progression, and survival. Additionally, the cost-effectiveness of the exercise program is assessed. Adherence and safety are monitored throughout the intervention period.DiscussionThis large randomized controlled trial will provide evidence regarding the (cost-) effectiveness of exercise during treatment of metastatic breast cancer. If proven (cost-)effective, exercise should be offered to patients with metastatic breast cancer as part of standard care.Trial registrationClinicalTrials.govNCT04120298. Registered on October 9, 2019.

The Influence of Medical Comorbidities on Survival Disparities in a Multiethnic Group of Patients with De Novo Metastatic Breast Cancer.

The influence of common medical comorbidities on mortality and racial/ethnic disparities in mortality among women with metastatic breast cancer remains largely unknown. In this longitudinal study, women with newly diagnosed stage IV breast cancer were identified in a large, diverse, integrated healthcare delivery system from January 2009 to December 2017 (n = 995) and followed through December 31, 2018, for all-cause (overall) and breast cancer-specific mortality via electronic health records. We computed overall and breast cancer-specific mortality rates by race/ethnicity and Elixhauser comorbidity index (ECI). Multivariable-adjusted hazard ratios (HR) assessing the influence of race/ethnicity and comorbidity status on overall and breast cancer-specific mortality were estimated using proportional hazards regression adjusted for age, breast cancer subtype, geocoded income, and palliative cancer treatments. Nearly 17% of this cohort had diabetes and 45% had hypertension. Overall, 644 deaths occurred in the cohort (median follow-up time of 1.8 years), of which 88% were breast cancer related. The risk of overall mortality was increased in Asian/Pacific Islander (PI; adjusted HR = 1.45; 95% CI, 1.10-1.92) and African American/Black women (adjusted HR = 1.34; 95% CI, 1.02-1.76) when compared with white women. Women with more comorbidities (ECI ≥ 5) had more than 3-fold higher overall mortality rate than those without any comorbidities [602/1,000 person-year (PY) vs. 175/1,000 PY]. Similar associations were found for breast cancer-specific mortality. Medical comorbidities are associated with an increased risk of overall mortality among women with de novo metastatic disease and may influence racial/ethnic disparities in mortality. Optimizing the management of medical comorbidities in metastatic breast cancer patients may also help reduce disparities in breast cancer-related mortality.

Abstract 3449: Radiation therapy for bridging and improving CAR-T cells therapy

Abstract CD19-targeted chimeric antigen receptor (CAR) T cells have transformed the treatment of patients with relapsed or refractory CD19-positive hematologic malignancies. However, a significant subset of these patients either fails to respond or eventually relapses. Moreover, patients who are candidates for CART-19 therapy often have symptomatic disease that requires some form of treatment to support them during the manufacture period. An ideal bridging therapy would simultaneously both (1) sensitize the tumor to CART-19 attack to increase antitumor control and (2) debulk the disease during manufacture. Radiotherapy (RT) is an established curative and palliative cancer treatment regimen, with approximately half of cancer patients with solid tumors receiving RT some time during their disease. Several reports have underscored the existence of threshold doses (and regimens) that are able to switch on different damage programs that profoundly affect responses to therapy by eliciting potent immune modulatory effects, prompting immunologically mediated tumor cell death. These effects have been attributed to multiple pathways, including the activation of the cGMP-cAMP Synthetase (cGAS), Stimulator of Interferon Genes (STING) pathway with Type I Interferons expression, and tumor associated antigen (TAA) cross priming with anti-tumor CD8+ T cell elicitation, ultimately inducing “abscopal” effects. By virtue of the immunomodulatory effects of RT, we hypothesize that RT could serve as a successful bridging strategy for CAR T-cell therapy. To investigate this hypothesis we established the A20 Lymphoma CART-19 therapy mouse model in our lab and use it to perform preliminaries experiments. A20 cells were implanted into both flanks of the animals. Mimicking human immune adjuvant dose used in our institute for RT bridging, 20 days after the A20 challenge we RT treated one of the two tumors using a dose of 8Gy divided in two fractions of 4Gy each. Twenty-four hours later 1x10ep6 CART-19 cells were infused intravenously. While the effects of RT in combination with CART-19 have similar impact on the tumor growth of the irradiated mass a significant increase of the antitumor effects of the single therapy was observed on the non-irradiated tumor. FACS studies demonstrated heavy leukocytes infiltration with increased presence of infused CART-19 as well indigenous T cells. To investigate possible molecular mechanisms involved in the increased effects on the non-irradiated tumor, we perform a qPCR array and observed increased expression of genes linked to cross priming, including IFN type I and Batf3. A20 cells express the ectopic retroviral antigen gp70 with well characterized AH1 immune-dominant epitope. AH1 tetramer staining on infiltrating T cells demonstrated increase staining in tumor from mice treated with the combination. Overall these results suggest RT may serve as optimal debulking and adjuvant bridging therapy for CAR-T cells therapy. Citation Format: Nektarios Kostopoulos, Costanitnos Koumeins, John P. Plastaras, Stephen J. Schuster, Andrea Facciabene. Radiation therapy for bridging and improving CAR-T cells therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3449.

Impact of Endoluminal Radiofrequency Ablation on Immunity in Pancreatic Cancer and Cholangiocarcinoma

Radiofrequency ablation (RFA) is a mini-invasive loco-regional ablation technique that is increasingly being used as a palliative treatment for pancreatic cancer and cholangiocarcinoma. Ablation-triggered immune system stimulation has been proposed as a mechanism behind the systemic effects of RFA. The aim of our study was to investigate the immune response to endoluminal biliary RFA. Peripheral blood samples were collected from patients with pancreatic cancer and cholangiocarcinoma randomised to receive endoluminal biliary radiofrequency ablation + stent (19 patients) or stent only (21 patients). We observed an early increase in IL-6 levels and a delayed increase in CXCL1, CXCL5, and CXCL11 levels as well as an increase in CD8+ and NK cells. However, these changes were not specific to RFA treatment. Explicitly in response to RFA, we observed a delayed increase in serum CXCL1 levels and an early decrease in the number of anti-inflammatory CD206+ blood monocytes. Our study provides the first evidence of endoluminal biliary RFA-based regulation of the systemic immune response in patients with pancreatic cancer and cholangiocarcinoma. These changes were characterised by a general inflammatory response. RFA-specific activation of the adaptive immune system was not confirmed.

Implementation of radiation segmentectomy for early-stage hepatocellular carcinoma

The findings from the RASER study, reported by Edward Kim and colleagues,1 highlight the versatility of radioembolisation, which has evolved from a historically palliative lobar cancer treatment into a segmental, ablative, therapy with curative intent. This paradigm shift began in 2016, with the PREMIERE trial,2 a single-centre, randomised trial for unresectable hepatocellular carcinoma not amendable to thermal ablation. PREMIERE showed a significant time-to-progression (TTP) advantage of segmental radioembolisation versus conventional chemoembolisation.

244P The incidence of infusion related reactions with trastuzumab-emtansine

Ado-trastuzumab-emtansine (T-DM1) is licensed as palliative and adjuvant treatment for breast cancer. The recommendation is for post-infusion observation of 90 minutes following cycle 1, and 30 minutes for subsequent cycles, owing to the risk of hypersensitivity reactions. The need for observation has significant implications for oncology day unit capacity and patient time in hospital. This study aimed to evaluate the rate and severity of trastuzumab-emtansine infusion reactions in our cohort of patients, to determine if shorter observation times would be safe.

Advances of Patient-Derived Organoids in Personalized Radiotherapy.

Patient-derived organoids (PDO), based on the advanced three-dimensional (3D) culture technology, can provide more relevant physiological and pathological cancer models, which is especially beneficial for developing and optimizing cancer therapeutic strategies. Radiotherapy (RT) is a cornerstone of curative and palliative cancer treatment, which can be performed alone or integrated with surgery, chemotherapy, immunotherapy, or targeted therapy in clinical care. Among all cancer therapies, RT has great local control, safety and effectiveness, and is also cost-effective per life-year gained for patients. It has been reported that combing RT with chemotherapy or immunotherapy or radiosensitizer drugs may enhance treatment efficacy at faster rates and lower cost. However, very few FDA-approved combinations of RT with drugs or radiosensitizers exist due to the lack of accurate and relevant preclinical models. Meanwhile, radiation dose escalation may increase treatment efficacy and induce more toxicity of normal tissue as well, which has been studied by conducting various clinical trials, very expensive and time-consuming, often burdensome on patients and sometimes with controversial results. The surged PDO technology may help with the preclinical test of RT combination and radiation dose escalation to promote precision radiation oncology, where PDO can recapitulate individual patient’ tumor heterogeneity, retain characteristics of the original tumor, and predict treatment response. This review aims to introduce recent advances in the PDO technology and personalized radiotherapy, highlight the strengths and weaknesses of the PDO cancer models, and finally examine the existing RT-related PDO trials or applications to harness personalized and precision radiotherapy.

Utility and safety of the self-expandable metallic colonic stent in Japanese patients who received systemic chemotherapy or palliative treatment for obstructive primary advanced colorectal cancer: A retrospective single-center medical chart evaluation.

Background and AimThe present study aimed to compare the utility and safety of the colonic self‐expandable metallic stent between patients with obstructive primary colorectal cancer who underwent chemotherapy or palliative treatment care and patients bridging for surgery.MethodsThe cases of 71 patients with colonic obstructive stenosis and in‐dwelling stents who were hospitalized between May 2012 and April 2020 at Karatsu Red Cross Hospital were retrospectively analyzed. The patients were classified into three groups: bridging for curative surgery (group I), receiving systemic chemotherapy (group II‐A), and receiving only palliative treatment (group II‐B). Technical and clinical success rates and complication rates after stenting were evaluated.ResultsNo significant differences were observed in the technical (procedure) success rates (group I: 100%; group II, 97.6% [II‐A: 100%; II‐B: 95.8%]). The total clinical success rate was 85.9% (61/71) and did not vary significantly among the groups (group I: 82.8%; group II 88.0% [II‐A: 83.3%; II‐B: 91.6%]). No significant differences were observed in the early complication rates between groups I and II and in the late complication rates between groups II‐A and II‐B. Nutrition status, general condition, tumor staging, and 1‐year survival were poorer in group II than in group I.ConclusionThe findings show that colonic stenting for malignant obstruction was performed successfully and safely both in patients who received systemic chemotherapy or palliative therapy and in patients bridging for curative surgery, regardless of risk status for malnutrition, poor general condition, cancer stage progression, and short survival.

Efficacy of open dialogue about complementary and alternative medicine compared with standard care in improving quality of life in patients undergoing conventional oncology treatment (CAMONCO 2): protocol for a randomised controlled trial

IntroductionComplementary and alternative medicine (CAM) has been shown to reduce symptoms and adverse effects and improve quality of life of patients undergoing conventional oncology treatment, but CAM might also cause...