Palliative Therapy Research Articles

SCOPE OF AYURVEDA IN THE MANAGEMENT OF KUSHTHA (SKIN DISEASES)

Background: Skin disorders are multi-faceted and may have their origin in allergy, autoimmunity, and hereditary. Ayurveda describes skin disorders under the umbrella of Kushtha, a disease characterized by the derangement of the skin. When we take into account the prevalence of different diseases, over 20% of all people seeking medical attention each year are suffering from skin disorders globally. Kushtha is categorized as Maha Kushtha and Kshudra Kushtha by all Acharyas depending on the severity of the symptoms and its prognosis. Many different etiological factors and disease management strategies are described in the Ayurvedic system of medicine. Aim: To assess the scope of Ayurveda in the management of skin diseases. Material & Methods: Different classical Ayurvedic texts, websites, journals and research articles were referred in the above context. Discussion & Conclusion: Kushtha arises from the vitiation of Tridosha and Twak, Rakta, Mamsa and Lasika. Thus the management for Kushtha is based on the involvement of Dosha and Dushya. Though some treatment modalities are condition-specific, the fundamental principle of treatment is consistent with all forms of Kushtha. Acharya have emphasized the significance of Shodhana (detoxification) therapy to eliminate the morbid Dosha from the body, and Raktamokshana to expel Dushita Rakta which is the key Dushya in the pathology of Kushtha. The Shamana (palliative) therapy comprises both internal and external medications viz. Rasa Aushadhi, Churna, Kwath, Asav, Arishta, Guggulu, Ghrita, and Malhara, Tail, Lepa. Dietary management, Dincharya, Ritucharya, Rasayana therapy, and Sadvritta are given immense importance in Ayurveda to preserve good health and prevention of diseases. This wholesome viewpoint of detoxification, palliative care and lifestyle modification needs to be analyzed to develop guidelines for the management of skin diseases based on Ayurveda principles.

Echocardiography-Guided Radiofrequency Ablation for Cardiac Tumors

BackgroundPatients with cardiac tumors may present challenges for surgical resection due to poor clinical condition. Echocardiography-guided transapical radiofrequency ablation for cardiac tumors (TARFACT) potentially offers a less invasive palliative therapy option. ObjectivesThis study aimed to evaluate the safety and efficacy of TARFACT. MethodsFive patients with cardiac tumors (mucinous liposarcoma, myocardial hypertrophy with inflammatory cell infiltration mass, fibrous tissue tumor hyperplasia, myocardial clear cell sarcoma, and cardiac rhabdomyoma) were included. All patients underwent TARFACT and were assessed with electrocardiogram, echocardiographic imaging, biochemical analysis, and pathological confirmation. ResultsThe median follow-up for all patients was 9 (range 4-12) months. Three surviving patients were alive at their last follow-up (9, 12, and 12 months, respectively), whereas 2 patients with late-stage tumors survived 6 months and 13 months after TARFACT, respectively. After TARFACT, all patients showed significant reductions in tumor size: the mean length decreased from 6.7 ± 2.0 cm to 4.7 ± 1.8 cm (P = 0.007); and the mean width decreased from 5.0 ± 2.1 cm to 2.5 ± 0.7 cm (P = 0.041). NYHA functional class also improved: median (IQR) decreased from 3.0 (1.5) to 2.0 (1.0) (P = 0.038), Peak E-wave on echocardiography showed a mean increase from 64.4 ± 15.7 cm/s to 76.6 ± 18.6 cm/s (P = 0.008), and NT-pro BNP levels had a median (IQR) reduction from 115.7 (252.1) pg/mL to 55.0 (121.6) pg/mL (P = 0.043). ConclusionsTARFACT is a novel palliative treatment option for cardiac tumors, reducing accessible tumors and improving clinical symptoms in a preliminary group of patients. (Cardiac Tumors Interventional [Radio Frequency/Laser Ablation] Therapy [CTIH]; NCT02815553)

Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy.

This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy. We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data. Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival. While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer's clonal evolution. Additionally, baseline-ctDNA's VAF values were prognostic after treatment.

Implementation of a simulation free palliative Radiation Therapy pathway: An inter-professional collaborative project

The Western New South Wales Local Health District (WNSWLHD) has a significant footprint within the state of New South Wales (NSW). Due to the significant size of the WNSWLHD, patients residing in the local health district face many barriers to receiving Radiation Therapy. The inter-professional collaboration behind the successful implementation and evaluation of a simulation free pathway for palliative Radiation Therapy in WNSWLHD will be explored within this narrative. The process known in WNSWLHD as Medical Imaging Simulated Radiation Therapy (MISRT) removes the need for a computed tomography (CT) simulation and allows for palliative Radiation Therapy to be planned on previously acquired diagnostic CT imaging. The implementation of MISRT has required significant inter-professional collaboration. This also extends to inter-centre partnership, intra-district cooperation with Medical Imaging and inter-discipline teamwork amongst Radiation Oncologists, Radiation Oncology Medical Physicists, Radiation Oncology Nursing and Radiation Therapists. The impact and involvement of the inter-disciplinary teamwork will be explored. The methods of implementing MISRT will be outlined covering changes to standard workflow, educational requirements and inclusion criteria. The evaluation of the implementation will also be covered with two evaluation surveys being conducted. Inter-professional communication, education, teamwork and collaboration is highlighted to demonstrate improving access to quality care in a rural and regional healthcare setting whilst reducing known barriers to accessing Radiation Oncology.

Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for distal cholangiocarcinoma: An international multicentre retrospective cohort study

IntroductionPatients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA. Materials and methodsPatients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence. ResultsIn the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion. ConclusionTwo thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.

Atypical Teratoid/Rhabdoid Tumor with Retained SMARCB1 (INI1) Expression and Rare SMARCA4 Gene Mutation: A Case Report of a Pediatric Patient

Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive tumors of the central nervous system (CNS), accounting for 1–3% of all pediatric CNS tumors. In general, AT/RTs are associated with biallelic inactivation of SMARCB1, resulting in the loss of expression of the integrase interactor 1 (INI1) protein. In this report, we describe the clinical course of an infant patient who presented with fatigue, postprandial vomiting, and disability of left side movement. Histological examination revealed classical features indicative of rhabdoid tumors, yet an atypical immunohistochemical profile with preserved INI1 expression was observed. Molecular diagnostics further elucidated the presence of a heterozygous frameshift variant, SMARCA4 c.2693del, p.(Asn898Thrfs*12), underscoring the distinctive genetic foundations of the case. Surgical resection of the tumor was administered with subsequent chemotherapy to the patient, but the condition worsened dynamically, and a decision was made to give the patient palliative therapy. We report on a patient with AT/RT caused by a rare mutation of the SMARCA4 gene and an aggressive course of disease to provide more information and characteristics of these tumors.

A novel entity of massive multifocal osteolyses in the elderly

Osteolyses are common findings in elderly patients and most frequently represent malignant or locally aggressive bone tumors, infection, inflammatory and endocrine disorders, histiocytoses, and rare diseases such as Gorham-Stout syndrome. We here report on a novel entity of massive multifocal osteolyses in both shoulders, the right hip and left knee joint and the dens of an 83-year-old patient not relatable to any previously known etiopathology of bone disorders. The soft tissue mass is of myxoid stroma with an unspecific granulomatous inflammatory process, aggressively destroying extensive cortical and cancellous bone segments and encroaching on articulating bones in diarthrodial large joints. Radiological, nuclear medical, serological, histological, and immunohistochemical analyses were incapable of further classifying the disease pattern within the existing scheme of pathology. Quantitative polymerase chain reaction and next generation sequencing revealed that mutations are not suggestive of any known hereditary or acquired bone disease. Possible treatment options include radionuclide therapy for pain palliation and percutaneous radiation to arrest bone resorption while surgical treatment is inevitable for pathological fractures. This case study shall increase the awareness of the musculoskeletal community and motivate to collect further information on this rare but mutilating disorder.

National trends in the treatment of adult diffuse midline gliomas: a rare clinical scenario.

Diffuse midline gliomas (DMG) include all midline gliomas with a point mutation to the histone H3 gene resulting in the substitution of a lysine with a methionine (K27M). These tumors are classified as World Health Organization grade 4 with a mean survival between 9- and 19-months following diagnosis. There is currently no standard of care for DMG, and palliative radiation therapy has been proven to only extend survival by months. Our current study aims to report current treatment trends and predictors of the overall survival of DMG. We searched the National Cancer Database for adult patients treated for DMG from 2016 to 2020. Patients were required to have been treated with primary radiation directed at the brain with or without concurrent chemotherapy. Univariable and multivariable Cox regressions were used to determine predictors of overall survival. Of the 131 patients meeting the inclusion criteria, 113 (86%) received radiation and chemotherapy. Based on multivariable Cox regression, significant predictors of survival were Charlson-Deyo comorbidity index and race. Patients with a Charlson-Deyo score of 1 had 2.72 times higher odds of mortality than those with a score of 0. Patients not identifying as White or Black had 2.67 times higher odds of mortality than those identifying as White. The median survival for all patients was 19 months. Despite being considered ineffective, chemotherapy is still administered in most adult patients diagnosed with DMG. Significant predictors of survival were Charlson-Deyo comorbidity index and race.

Diagnostic CT-Enabled Planning (DART): Results of a Randomized Trial in Palliative Radiation Therapy

Using diagnostic computed tomography (dCT) scans instead of CT simulation (CTsim) scans can increase departmental efficiency and reduce patient burden. The goal of the DART trial was to assess the efficacy and acceptability of dCT-based planning workflows with a focus on patient experiences, plan deliverability and adequacy of target coverage, and workflows. Patients undergoing same-day CTsim and treatment for palliative radiation therapy to thoracic, abdominopelvic, or proximal limb targets with a recent dCT (within 28 days) in a reproducible position were eligible. After stratifying by target type (bone or soft tissue vs. visceral), participants were randomized (1:2 ratio) between CTsim-based (CTsim arm) vs. dCT-based planning (dCT arm). The primary endpoint was time in center (TIC), defined as total time spent in the cancer center on first day of treatment, from first radiation department appointment to first fraction completion. Secondary endpoints included plan deliverability, adequacy of target coverage, and stakeholder acceptability. Thirty-three patients (42 treatment sites) were enrolled between June 2022 and April 2023. The median age was 72 (interquartile range [IQR]: 67-78), 73% were male, and the most common primary cancers were lung (33%), prostate (24%), and breast (12%). The most common dose and fractionations were 8 Gy in 1 and 20 Gy in 5 fractions (50% and 43% of plans, respectively). TIC was 4.7 ± 1.1 hours (mean ± SD) in the CTsim arm vs. 0.41 ± 0.14 hours in the dCT arm (P < .001). All dCT plans were deliverable. All plans in both arms were rated as "acceptable" (80% CTsim; 81% dCT) or "acceptable with minor deviation" (20% CTsim; 19% dCT). Patient perception of acceptability was similar in both arms with the exception of time burden, which was rated as "acceptable" by 50% in the CTsim arm vs. 90% in the dCT arm (P = .025). dCT-based radiation planning substantially reduced TIC without detriment in plan deliverability or quality and had a tangible impact on patient experience with reduced patient-reported time burden.

Novel self-expandable stent–based endobiliary radiofrequency ablation for unresectable malignant biliary obstruction

Endobiliary radiofrequency ablation (RFA) is an emerging endoscopic palliative adjunctive therapy used for the local treatment of unresectable malignant biliary obstruction (MBO). However, irregular ablation ranges caused by insufficient electrode-to-bile duct contact pose a significant obstacle. We investigated the feasibility of a self-expandable stent (SES)-based electrode with a customized RFA generator in the porcine liver and common bile duct (CBD). An SES-RFA system with polarity switching was developed to perform endobiliary RFA. The ablation ranges of 20 ablation protocols were evaluated to validate the feasibility of the newly developed RFA system in the porcine liver. Nine of 20 ablation protocols were selected for evaluation in the porcine CBD with cholangiography, endoscopy, and histologic and immunohistochemical analysis. The SES-RFA system with polarity switching was successfully constructed and demonstrated high accuracy and reproducibility. The ablation area was clearly identified between the 2 SESs. The ablation ranges and degree of mucosal damage, including terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling-positive and heat shock protein 70-positive depositions, increased proportionally with ablation protocols in the porcine liver and CBD (all P< .05). Ablation length and depth linearly increased with ablation protocols from 8.74 ± .25 to 31.25 ± .67mm and 1.61 ± .09 to 11.94 ± .44mm, respectively. The SES-RFA system with polarity switching between electrodes provided an even circumferential area of ablation and enhanced ablation depth between the electrodes. This novel endobiliary RFA system is a promising modality for local ablation in patients with unresectable MBO.

Disease-State Understanding and Experience of Patients Receiving Continuous Intravenous Inotropic Support as Palliative Therapy: A Multicenter Survey.

Background: The use of continuous intravenous inotropic support (CIIS) as palliative therapy in patients with advanced heart failure (HF) has increased over the past decade. CIIS improves New York Heart Association (NYHA) functional class but does not impact survival. Objective: The objective of this study was to examine patients' understanding of the therapeutic intent of CIIS, prognostic awareness, and quality of life with CIIS. Design: We conducted a prospective, cross-sectional, multicenter study of patients with advanced HF receiving CIIS as palliative therapy between 2020 and 2022. Settings/Subjects: An investigator-developed survey instrument was administered to outpatients on CIIS in the United States via telephone. Measurements: Survey data were analyzed using descriptive and inferential statistics. Results: Forty-eight patients, 63% male, 81% African American/Black, with a mean age of 68.9 (standard deviation 12.3) years, participated in this study. The majority of patients responded that they expected CIIS to make them feel better (79%) and increase longevity (75%), but few expected that CIIS would cure their HF (19%). Patients described their overall quality of life on CIIS as not better/worse (19%), somewhat better (46%), and significantly better (35%) and reported high treatment satisfaction (87% were at least somewhat satisfied). Conclusions: In this study, patients report improved quality of life with CIIS as palliative therapy. Patients on CIIS as palliative therapy expected increased survival on CIIS, which is incongruent with current evidence. Further studies on how we can improve care processes so that patients have accurate prognostic and disease-state awareness, and receive goal concordant care, are warranted.

Management of Shushka Vicharchika through Shamana Aushadhis: a case report

Abstract Introduction: Among the Kshudra Kustha, Vicharchika exhibits symptoms such as Kandu (itching), Shrava (discharge), and Shyava Varna (blackish discoloration). Vicharchika is one among the Kshudra Kustha, which continues for a long period and has a propensity for aggravation. Most often, Vicharchika patients who do not respond well to contemporary medical care seek treatment from Ayurveda, hoping for a complete recovery from their illness. Materials and Methods: An 85-year-old male patient with signs and symptoms corresponding to Vicharchika was treated with Shamana Aushadhis (palliative therapy). Result: A remarkable improvement in the condition was observed in a span of 21 days. Discussion: Chronic skin diseases can be managed with Ayurvedic medications and the current article represents detailed management of it.

Posterior-only 2-level vertebrectomy and fusion in a medically complex patient with lumbar metastasis: illustrative case.

Spinal metastases are commonly seen in patients with cancer and often indicate a poor prognosis. Treatment can include curative or palliative surgery, chemotherapy, and radiation therapy. The surgical approach varies widely on the basis of the affected region of the spine, the location of the tumor (anterior versus posterior), the goal of surgery, the health of the patient, and surgeon preference. The authors present a case of a 68-year-old male with intractable lower-back pain and substantially diminished ambulation. Diagnostic imaging revealed a lumbar metastasis from a cholangiocarcinoma primary at L2-3 (4.5 cm anteroposterior × 5.7 cm transverse × 7.0 cm craniocaudal). The patient underwent a 2-level vertebrectomy with expandable cage placement and T10 to S2 fusion via a posterior-only approach. The patient regained much of his mobility and quality of life after the surgery. Although this was a high-risk surgery, the authors show that a posterior-only approach can be used for lumbar vertebrectomies and fusion when necessary. Palliative surgeries carrying a high risk, especially in the setting of a limited prognosis, should include multidisciplinary deliberations and a thorough discussion of the risks and outcome expectations with the patient.

Real-world treatment patterns and clinical outcomes in patients with stage III NSCLC in Korea: The KINDLE study.

KINDLE-Korea is part of a real-world KINDLE study that aimed to characterize the treatment patterns and clinical outcomes of patients with stage III non-small cell lung cancer (NSCLC). The KINDLE was an international real-world study that explores patient and disease characteristics, treatment patterns, and survival outcomes. The KINDLE-Korea included stage III NSCLC patients diagnosed between January 2013 and December 2017. A total of 461 patients were enrolled. The median age was 66 years (range: 24-87). Most patients were men (75.7%) with a history of smoking (74.0%), stage IIIA NSCLC (69.2%), and unresectable disease (52.9%). A total of 24.3% had activating EGFR mutation and 62.2% were positive for PDL1 expression. Broadly categorized, 44.6% of the patients received chemoradiation (CRT)-based therapy, 35.1% underwent surgery, and 20.3% received palliative therapies as initial treatment. The most commonly adopted approaches for patients with stage IIIA and IIIB disease were surgery and CRT, respectively. The median PFS was 15.2 months and OS was 66.7 months. Age >65 years, adenocarcinoma histology, and surgery as the initial treatment were significantly associated with longer OS. This study revealed the heterogeneity of treatment patterns and survival outcomes in patients with stage III NSCLC before durvalumab consolidation came into clinical practice. There is an unmet need for patients who are not eligible for surgery as an initial therapy. Novel therapeutic approaches are highly warranted to improve clinical outcomes.

Salvage high-intensity focused ultrasound (S-HIFU) for recurrence after primary radiotherapy of prostate cancer

ObjectivesTo evaluate functional and oncological outcomes of salvage high-intensity focal ultrasound (S-HIFU) after external beam radiotherapy (EBRT) failure in prostate cancer (PCa) patients. MethodsThis single-center study included patients who underwent S-HIFU for local recurrence after EBRT between 2006 and 2023. Cancer-specific survival, metastasis-free survival and progression-free survival were illustrated using Kaplan–Meier curves. Disease progression was defined by one of the following criteria: increase of 2ng/mL or more above the PSA nadir, positive post-S-HIFU biopsy or initiation of androgen deprivation therapy (ADT). Multivariable Cox proportional hazards model was used to identify predictors of disease progression after S-HIFU. ResultsA total of 52 S-HIFU sessions for 48 patients were performed. Median time between EBRT and S-HIFU was 6.5 years. Median PSA before S-HIFU was 3.2ng/mL and median PSA nadir after S-HIFU was 0.58ng/mL. A total of 39 (81.3%) complications was recorded, including 3 (6.3%) high grade complications according to the Clavien-Dindo classification. After a median follow-up period of 6 years, 14 (29.2%) patients developed metastatic disease. Eighteen (37.5%) patients had no recurrence, whereas 30 (62.5%) patients received ADT for disease progression. The estimated 5-yr cancer-specific survival (CSS), metastasis-free survival (MFS) and progression-free survival rates (PFSR) were 100%, 79.9% (95% CI 67–92) and 41.2% (95% CI 74–96), respectively. The estimated 10-yr CSS, MFS and PFSR were 80% (95% CI 45–100), 50.7% (95% CI 19.4–82.1) and 14% (95% CI 10.8–45), respectively. The hazard of progression increased with the intermediate (HR 3.8; 95% CI 0.99 to 15; p=0.049) and high pre-EBRT d’Amico-s risk group (HR 4.1; 95% CI 0.98 to 16.2; p=0.050). Also, the time between EBRT and S-HIFU was significantly associated with risk of progression (HR 0.61; 95% CI 0.43 to 0.86; p=0.004). No significant difference linked to the disease progression (DP) risk was found between focal vs whole-gland treatment (p=0.70). ConclusionPhysicians should consider HIFU as a local salvage treatment after failed EBRT, thus avoiding or delaying palliative androgen deprivation therapy. Further studies are needed to improve patient selection for this therapy. Level of evidence4.

Cost and value of cancer medicines in a single-payer public health system in Ontario, Canada: a cross-sectional study

The financial impact of cancer medicines on health systems is not well known. We describe temporal trends in expenditure on cancer medicines within the single-payer health system of Ontario, Canada, and the extent of clinical benefit these treatments offer. In this cross-sectional study, we identified cancer medicines and expenditures from formularies and costing databases (the New Drug Funding Program, Ontario Drug Benefit Program, and The High-Cost Therapy Funding Program) during 10 consecutive years (April 1, 2012, to March 31, 2022) in Ontario, Canada. For intravenous medicines, we applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) to identify expenditures associated with substantial clinical benefit. We also identified treatments associated with improved overall survival or quality of life. 69 intravenous and 98 oral or injectable medicines were funded during 2012-22. Annual expenditure on cancer medicines increased by approximately 15% per year during 2012-22; the increase was more rapid in the most recent 4 years. Total expenditure on cancer medicines in the 2021-22 financial year was CA$1·7 billion. Immune checkpoint inhibitors were the single biggest expense by class ($284 million), representing 17% of the entire cancer medicine annual budget. Drugs with the highest individual costs were lenalidomide ($178 million) and pembrolizumab ($163 million), each accounting for around 10% of the entire budget. 29 (76%) of 38 indications eligible for ESMO-MCBS scoring met the threshold for substantial clinical benefit. Eight (21%) indications had no randomised trial evidence of improved overall survival, and only four (11%) were associated with improved QOL. $346 million (67% of the expenditure on intravenous cancer medicines) was spent on drugs that improved median overall survival by more than 6 months, $82 million (16%) was spent on medicines with overall survival gains of 3-6 months, and $32 million (6%) was spent on medicines with overall survival gains of less than 3 months. $53 million (10%) was spent on medicines with no established improvement in overall survival. Costs of cancer medicines to the Canadian health system are increasing rapidly. Most funded indications met thresholds for substantial clinical benefit and two-thirds of the expenditure were for medicines that improve survival by more than 6 months. Whether this cost trajectory can be maintained in a sustainable, equitable, high-quality health system is unclear. Efforts are needed to ensure the price of medicines with substantial benefit is affordable and funding of treatments with very modest benefit might need to be re-assessed, particularly when alternative supportive and palliative therapies are available. None.

Comparative Effectiveness and Safety of Intermittent, Repeated, or Continuous Use of Levosimendan, Milrinone, or Dobutamine in Patients With Advanced Heart Failure: A Network and Single-Arm Meta-analysis.

The aim of this study was to synthesize the available evidence regarding differences in the long-term safety and efficacy of intermittent, repeated, or continuous palliative inotropic therapy among patients with advanced heart failure. We systematically searched the PubMed, Embase, and Cochrane Library electronic databases, with a cutoff date of November 23, 2023, for studies reporting outcomes in adult patients with advanced heart failure treated with intermittent, repeated, or continuous levosimendan, milrinone, or dobutamine. Forty-one studies (18 randomized controlled trials and 23 cohort studies) comprising 5137 patients met the inclusion criteria. The results of the network meta-analysis of randomized controlled trials showed that levosimendan had significant advantages over milrinone or dobutamine in reducing mortality and improving left ventricular ejection fraction. A single-arm meta-analysis also indicated that levosimendan had the lowest mortality and significantly improved B-type brain natriuretic peptide and left ventricular ejection fraction. Regarding safety, hypotension events were observed more frequently in the levosimendan and milrinone groups. However, the current evidence is limited by the heterogeneity and relatively small sample size of the studies.

Chronological Course and Clinical Features after Denver Peritoneovenous Shunt Placement in Decompensated Liver Cirrhosis.

Refractory ascites affects the prognosis and quality of life in patients with liver cirrhosis. Peritoneovenous shunt (PVS) is a treatment procedure of palliative interventional radiology for refractory ascites. Although it is reportedly associated with serious complications (e.g., heart failure, thrombotic disease), the clinical course of PVS has not been thoroughly evaluated. To evaluate the relationship between chronological course and complications after PVS for refractory ascites in liver cirrhosis patients. This was a retrospective study of 14 patients with refractory ascites associated with decompensated cirrhosis who underwent PVS placement between June 2011 and June 2023. The clinical characteristics, changes in cardiothoracic ratio (CTR), and laboratory data (i.e., brain natriuretic peptide (BNP), D-dimer, platelet) were evaluated. Follow-up CT images in eight patients were also evaluated for ascites and complications. No serious complication associated with the procedure occurred in any case. Transient increases in BNP and D-dimer levels, decreased platelet counts, and the worsening of CTR were observed in the 2 days after PVS; however, they were improved in 7 days in all cases except one. In the follow-up CT, the amount of ascites decreased in all patients, but one patient with a continuous increase in D-dimer 2 and 7 days after PVS had thrombotic disease (renal and splenic infarction). The mean PVS patency was 345.4 days, and the median survival after PVS placement was 474.4 days. PVS placement for refractory ascites is a technically feasible palliative therapy. The combined evaluation of chronological changes in BNP, D-dimer, platelet count and CTR, and follow-up CT images may be useful for the early prediction of the efficacy and complications of PVS.

Abstract 966: Longitudinal comparative analysis of circulating tumor DNA and matched tumor tissue DNA in patients with metastatic colorectal cancer receiving palliative first-line systemic anti-cancer therapy

Abstract Background: Plasma circulating tumor DNA (ctDNA) analysis has become an attractive method for precision oncology. This study compared mutational landscapes of ctDNA with matched tumor tissue DNA (ttDNA) to explore clinical applicability and to better understand clonal evolution in patients with metastatic colorectal cancer receiving palliative first-line systemic anti-cancer therapy (SACT). Methods: We performed unique molecular identifier-based targeted sequencing of 88 cancer-associated genes using the following samples: ttDNA, germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). Results: Of the 208 consecutively enrolled patients, 84 were selected (41 males; median age 59, ranging from 35 to 90) with access to all four samples. Excluding duplicated mutations, a total of 202 driver mutations were discovered in 34 genes. ttDNA exhibited the highest occurrence of mutations (N=232), followed by baseline-ctDNA (N=155) and PD-ctDNA (N=117). Genotype concordance for the ten most mutated genes was highest between baseline-ctDNA and PD-ctDNA, at 94.3%, while the concordance rates for ttDNA were 85.5% with baseline-ctDNA and 83.6% with PD-ctDNA. Overall, 40 of the 84 patients (47.6%) benefited from sequencing ctDNA in addition to ttDNA as it identified additional mutations. Compared to ttDNA and baseline-ctDNA, PD-ctDNA identified 13 novel mutations in ten patients (11.9%). Notably, 7 mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, patients with maximal variant allele frequency (VAF) values of &amp;gt;0.059 showed significantly worse progression-free survival (median 10.5 vs. 17.1 months, P=0.036) and overall survival (median 18.1 vs. 40.3 months, P=0.010). Moreover, overall survival was significantly worse in those with higher VAF values of APC (median 18.1 vs. 36.8 months, P=0.012), TP53 (median 24.7 vs. 40.3 months, P=0.012), and KRAS (median 13.7 vs. 27.6 months, P=0.005) mutations. Conclusions: While ttDNA remains more sensitive than ctDNA, our unique molecular identifier-based ctDNA platform demonstrated the validity and potential value when ttDNA was unavailable. Furthermore, post-SACT analysis of PD-ctDNA revealed new pathogenic mutations, indicating the clonal evolution of cancer. In addition, the VAF values of baseline-ctDNA predicted prognosis after SACT. Citation Format: Ji-Won Kim, Seung-been Lee, Hong-Geun Kim, Sung-Hyun Hwang, Kui-Jin Kim, Ju Hyun Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Koung Jin Suh, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Jee Hyun Kim, Nak-Jung Kwon, Keun-Wook Lee. Longitudinal comparative analysis of circulating tumor DNA and matched tumor tissue DNA in patients with metastatic colorectal cancer receiving palliative first-line systemic anti-cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 966.

Diagnosis of Metastatic Non-Small Cell Lung Cancer during Hospitalization: Missed Opportunity for Optimal Supportive Care?

The usual workup for patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) occurs in the ambulatory setting. A subset of patients present with acute care needs and receive the diagnosis while hospitalized. Palliative therapies are typically initiated when patients are outpatients, even when diagnoses are made when they are inpatients. Lengthy admission, rehabilitation needs after discharge, and readmissions are possible barriers to timely and adequate outpatient follow-up. The outcomes for these patients diagnosed in the hospital are not well characterized. We hypothesized that patients have been ill-served by current treatment patterns, as reflected by low rates of cancer-directed treatment and poor survival. We performed a retrospective study of new inpatient diagnoses of metastatic NSCLC at our institution between 1 January 2012 and 1 January 2022. The primary outcome was the proportion of patients ultimately receiving cancer-directed therapy. Other outcomes included time to treatment, use of targeted therapy, palliative care/hospice utilization, and overall survival (OS). Seventy-three patients were included, with a median age of 57 years. Twenty-seven patients (37%) ultimately received systemic therapy with a median time from diagnosis to treatment of 37.5 days. Overall, 5.4% patients died while admitted, 6.8% were discharged to a hospice, 21.9% were discharged to a facility, and 61.6% were discharged home. Only 20 patients (27%) received palliative care consultation. The median OS for our entire population was 2.3 months, with estimated 6-month and 1-year OS rates of 32% and 22%, respectively. Patients with new inpatient diagnoses of metastatic NSCLC have extremely poor outcomes. Current management strategies resulted in few patients starting systemic therapy, yet most of the patients did not receive palliative care or hospice involvement. These findings demonstrate that there is a high unmet need to optimally support and palliate these patients.