Cost-efficiency and budget-neutral expanded access modeling of pembrolizumab versus the novel PD-1 inhibitor toripalimab in locally advanced or metastatic nonsquamous non-small cell lung cancer.

AIMS: To estimate in a panel of patients with locally advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with a programmed death receptor-1 inhibitor in the US in 2024 (1) the cost-efficiency of toripalimab regimens compared to pembrolizumab regimens; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens from accrued savings. METHODS: Simulation modeling of toripalimab + pemetrexed + carboplatin in nonsquamous NSCLC to a similar pembrolizumab regimen in a panel of 49,647 patients; utilizing two cost inputs (wholesale acquisition cost (WAC) at market entry and an estimated ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) plus administration costs over one and two years of treatment with treatment rates from 1%-10%. Scenario analyses with treatment durations equivalent to toripalimab and pembrolizumab trials' median PFS were also conducted. RESULTS: In the WAC-based models, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 49,647-patient panel, estimated 1-year savings range from $19,865,840 (1% treatment rate) to $198,658,399 (10% rate). Reallocating these savings permits budget-neutral expanded access to an additional 1,753 (1% rate) to 17,533 (10% rate) toripalimab maintenance cycles or to an additional 97 (1% rate) to 972 (10%) full 1-year toripalimab regimens with all agents. Two-year savings range from $38,628,022 (1% rate) to $386,280,221 (10%). Reallocating these efficiencies provides expanded access ranging from 3,409 (1% rate) to 34,093 (10%) additional toripalimab cycles or to 97 to 973 full 2-year regimens. The ex ante ASP model showed similar results as did the scenario analyses but at a lower magnitude than the base case. CONCLUSION: Toripalimab generates significant savings that enable budget-neutral funding for up to 17,533 [34,093] additional maintenance cycles over one year [two years] with toripalimab + pemetrexed in nonsquamous NSCLC, or 972 [973] full one-year [two-year] regimens.

An estimated 49,647 patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) will be treated with a PD-1 inhibitor in the US in 2024. Toripalimab, a PD-1 inhibitor recently approved by the US Food and Drug Administration for the treatment of nasopharyngeal carcinoma, has also been found to be beneficial in patients with nonsquamous NSCLC when used in combination with chemotherapy. We conducted an economic simulation of the costs of toripalimab + pemetrexed + carboplatin versus the costs of a similar regimen with the PD-1 inhibitor pembrolizumab in the treatment of patients with nonsquamous NSCLC. Our simulation models used two US cost inputs for toripalimab: the wholesale acquisition cost or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, a hypothetical toripalimab price point of 80% of the pembrolizumab ASP. We compared the savings in each scenario when between 1% and 10% of the 49,647 nonsquamous NSCLC patients are treated with the toripalimab regimen. We then evaluated how these savings could be re-allocated, without requiring extra funding, to provide more patients with access to toripalimab treatment on a budget-neutral basis. We found that, if 1% of new cases of advanced/metastatic nonsquamous NSCLC were treated with toripalimab for 1 year, these savings are enough to purchase up to 1,753 additional toripalimab maintenance cycles; or these savings could provide up to an additional 97 patients with full one-year regimens with all agents (toripalimab + chemotherapy). If 10% of new cases were treated with toripalimab for 1 year, the savings are enough to purchase up to 17,533 additional toripalimab maintenance cycles; or these savings could provide up to an additional 972 patients with full one-year regimens with all agents.

Budget impact analysis of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma.

AIM: To estimate the budget impact of adding a toripalimab regimen as a treatment option to the existing pembrolizumab regimen, both including gemcitabine and cisplatin, in untreated recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) using the published wholesale acquisition cost (WAC) and average sales price (ASP). METHODS: Budget impact analysis comparing a treatment mix "without" versus "with" the toripalimab regimen in the US eligible annual incident R/M NPC population, a 3-year time horizon, toripalimab/pembrolizumab market splits of 60/40 (Y1) and 80/20 (Y2/3), and medication adjustments for discontinuation or progression. Cost inputs included drugs, administration, and adverse event (AE) management. The models were replicated for a hypothetical 1-million-member health plan in which costs per-member-per-month (PMPM) and per-member-per-year (PMPY) were estimated. One-way (OWSA) and probabilistic sensitivity analyses (PSA) as well as scenario analyses were performed. RESULTS: In the "without" scenario, the 3-year WAC-based costs for the pembrolizumab regimen total $1,449,695,333 ($1,305,632,448 for treatment and $144,062,885 for managing AEs). In the "with" scenario, total 3-year costs for pembrolizumab decline to $380,012,135 with toripalimab adding $885,505,900 ($779,206,567 for treatment and $106,299,333 for AE management). Annual net savings range from $46,526,152 in 2024 to $71,194,214 in 2026, for 3-year savings of $184,177,298. Associated net savings in a 1-million-member health plan are $543,068 over 3 years with savings of $0.045 PMPM and $0.543 PMPY. The ASP-based model shows similar patterns with 3-year net savings of $174,235,983 in the US incident population and savings of $0.043 PMPM and $0.514 PMPY in a 1-million-member health plan. The PSA support base case findings; OWSA and scenario analyses reveal how parameter variability impacts results. CONCLUSION: Savings between $174 million and $184 million can be achieved from treating 60% of R/M NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen over a similar pembrolizumab regimen.

Toripalimab, a human monoclonal anti-body that targets PD-1, was recently approved by the US Food and Drug Administration (FDA) for the first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC), in combination with gemcitabine and cisplatin. We evaluated how much it would cost a payor to cover the FDA-approved toripalimab plus gemcitabine and cisplatin regimen (the toripalimab regimen) to a non-FDA-approved pembrolizumab plus gemcitabine and cisplatin regimen (the pembrolizumab regimen). With no trial data available for such pembrolizumab regimen, we assumed that it would be comparable to the toripalimab regimen in efficacy and safety. Our model adopted a 3-year time horizon and assumed a 60/40 market share split in year 1 and an 80/20 market split in years 2 and 3. It included two US cost inputs: the wholesale acquisition cost (WAC) or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, a toripalimab price point of 80% of the pembrolizumab ASP. We adjusted for patients whose cancer progressed or who discontinued treatment to determine the number of fully-treated-patient-equivalents. We found that treating 60% of NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen instead of the pembrolizumab regimen generates, for the entire adjusted patient population, savings ranging from $174 million when using ASP to $184 million when using WAC.

Phase Ib and pharmacokinetics study of alpelisib, a PIK3CA inhibitor, and capecitabine in patients with advanced solid tumors.

Background: This phase Ib study was performed to determine the safety of combination capecitabine with alpleisib (phosphatidylinositol 3-kinase catalytic subunit p110α blockade) and determine the maximal tolerated dose (MTD) and recommended phase ll dose (RP2D) of this combination regimen in patients with advanced solid tumors refractory to standard therapy. The synergistic anti-tumor activity and pharmacokinetics (PK) were investigated. Methods: Dose escalation phases were conducted in patients with advanced solid cancers who were refractory to standard therapy regardless of PIK3CA mutation. Patients were administered orally once daily alpelisib (200mg and 300mg) and twice daily capecitabine (850mg, 1000mg, 1250mg orally, days 1-14) every 3 weeks. Standard "3 + 3" dose escalation was used to define the MTD. The effect of alpelisib on the PK of capecitabine was assessed. Results: Patients with 6 colorectal cancer (three PIK3CA mutation) and 6 breast cancer (all PIK3CA mutation) were enrolled. The first three patients in dose level 0 (alpelisib 200mg daily, capecitabine 1,000 mg/m2 twice daily) had no dose-limiting toxicities (DLTs). In dose level 1 (alpelisib increased to 300 mg daily, capecitabine 1,000mg twice daily), one of six patients had DLT (grade (Gr) 3 hyperglycemia). When dose level 2 (alpelisib 300mg daily, capecitabine 1,250 mg/m2 twice daily) was expanded to 3 patients, no patients had DLTs. The combination of alpelisib 300mg daily and capecitabine 1,250 mg/m2 twice daily was declared as the MTD/RP2D in patients with advanced solid tumors. The most common AEs were Gr 1-3 hyperglycemia (75.0%). Frequent all-grade, treatment-related AEs included Gr 2-3 nausea (75.0%), Gr 1-2 diarrhea (50.0%), Gr 1-2 hand-foot syndrome (41.7%), Gr 1-2 anorexia (41.7%), Gr 2 mucositis (33.3%). Antitumor activity was observed in patients with PIK3CA mutant breast cancer (3 partial response and 3 stable disease of total 6 patients). Alpelisib exposure (Cmax and AUC0-12) was unaffected by concomitant capecitabine. There were no clinically relevant drug-drug interactions observed between alpelisib and capecitabine. Conclusions: The combination of alpelisib and capecitabine is generally tolerated, without pharmacokinetic interactions, and shows antitumor activity in patients with PIK3CA mutant advanced cancers.

Management of immune check-point inhibitor-associated colitis in patients with advanced metastatic cancers: A review article.

Immune check-point inhibitors (ICPi) are immunomodulating agents, which have revolutionized the management of advanced metastatic cancers. Being immunomodulating agents, they are predisposed to causing colitis. This descriptive review article emphasized on the management of ICPi-associated colitis in advanced metastatic cancers. We used PubMed, Google Scholar, Scopus, and Embase databases for literature review, and terminologies commonly searched were "management," "immune check-point inhibitors," "colitis," "metastatic," "cancers," "literature," and "review." We reviewed a total of 11 articles done in the last 15 years relevant to ICPi colitis and its management; all the articles showed that diarrhea and colitis are the most common adverse effects observed in patients on ICPi, but prior to establishing the diagnosis of ICPi-causing colitis, possibility of Clostridium difficle or cytomegalovirus infections should be ruled out. Once the diagnosis of ICPi colitis is established, treatment should be started depending upon the severity of colitis. In mild severity, discontinuation of ICPi can resolve the symptoms but, in most of the patients with moderate to high severity of colitis, corticosteroids are considered a cornerstone treatment. Patients unresponsive to steroid treatment should be re-evaluated for infections after which anti-TNF therapy-infliximab or vedolizumab, cyclosporine, mycophenolate mofetil-can be considered.

The impact of socioeconomic inequality on access to health care for patients with advanced cancer: A qualitative study.

Objective: In Canada, populations experiencing socioeconomic inequality have lower rates of access to screening and diagnosis and higher mortality rates than people from higher-income areas. Limited evidence exists concerning their experiences when living with advanced cancer. We explored how socioeconomic inequality shapes the experiences of patients with advanced cancer. Methods: We utilized a qualitative study design that combined tenets of hermeneutic phenomenological inquiry and critical theory. Four individuals with advanced cancer from low-income neighborhoods, three family members, and six cancer care providers were accrued through a tertiary cancer center in a western Canadian city. One-on-one interviews and brief notes were used for data collection. Data were analyzed through thematic analysis. Results: Three interrelated themes were identified: 'Lack of access to socioeconomic supports,' 'Gaps in access to health care resources and services,' and 'Limited access to symptom relief.' Patients experienced inadequate finances, housing, and transportation. Most patients lived alone and had limited family and social support. Patients reported lack of knowledge of available resources and health system navigation issues, including communication problems with providers and among levels of care. Cancer care providers and patients described issues achieving symptom relief as well as challenges associated with extensive disease. Conclusions: Study findings suggest that socioeconomic inequality interferes with the ability of persons with advanced cancer to access health care and contributes to less optimal cancer outcomes. Socioeconomic inequality may increase symptom severity. Findings call for the development of tailored interventions for populations with advanced cancer and socioeconomic inequality.

A Near-Infrared-II Excitable Pyridinium Probe with 1000-Fold ON/OFF Ratio for γ-Glutamyltranspeptidase and Cancer Detection.

Activity-based detection of γ-Glutamyltranspeptidase (GGT) using near-infrared (NIR) fluorescent probes is a promising strategy for early cancer diagnosis. Although NIR pyridinium probes show high performance in biochemical analysis, the aggregation of both the probes and parental fluorochromes in biological environments is prone to result in a low signal-to-noise ratio (SBR), thus affecting their clinical applications. Here, we develop a GGT-activatable aggregate probe called OTBP-G for two-photon fluorescence imaging in various biological environments under 1040 nm excitation. By rationally tunning the hydrophilicity and donor-acceptor strength, we enable a synergistic effect between twisted intramolecular charge transfer and intersystem crossing processes and realize a perfect dark state for OTBP-G before activation. After the enzymatic reaction, the parental fluorochrome exhibits bright aggregation-induced emission peaking at 670 nm. The fluorochrome-to-probe transformation can induce 1000-fold fluorescence ON/OFF ratio, realizing in vitro GGT detection with an SBR > 900. Activation of OTBP-G occurs within 1 min in vivo, showing an SBR > 400 in mouse ear blood vessels. OTBP-G can further enable the early detection of pulmonary metastasis in breast cancer by topically spraying, outperforming the clinical standard hematoxylin and eosin staining. We anticipate that the in-depth study of OTBP-G can prompt the development of early cancer diagnosis and tumor-related physiological research. Moreover, this work highlights the crucial role of hydrophilicity and donor-acceptor strength in maximizing the ON/OFF ratio of the TICT probes and showcases the potential of OTBP as a versatile platform for activity-based sensing.

Application of Transcriptome-Based Gene Set Featurization for Machine Learning Model to Predict the Origin of Metastatic Cancer.

Identifying the primary site of origin of metastatic cancer is vital for guiding treatment decisions, especially for patients with cancer of unknown primary (CUP). Despite advanced diagnostic techniques, CUP remains difficult to pinpoint and is responsible for a considerable number of cancer-related fatalities. Understanding its origin is crucial for effective management and potentially improving patient outcomes. This study introduces a machine learning framework, ONCOfind-AI, that leverages transcriptome-based gene set features to enhance the accuracy of predicting the origin of metastatic cancers. We demonstrate its potential to facilitate the integration of RNA sequencing and microarray data by using gene set scores for characterization of transcriptome profiles generated from different platforms. Integrating data from different platforms resulted in improved accuracy of machine learning models for predicting cancer origins. We validated our method using external data from clinical samples collected through the Kangbuk Samsung Medical Center and Gene Expression Omnibus. The external validation results demonstrate a top-1 accuracy ranging from 0.80 to 0.86, with a top-2 accuracy of 0.90. This study highlights that incorporating biological knowledge through curated gene sets can help to merge gene expression data from different platforms, thereby enhancing the compatibility needed to develop more effective machine learning prediction models.

Colon Cancer Metastasis to Spermatic Cord Presenting as an Inguinal Hernia.

Introduction: Inguinal hernias are very common. Their pathology and treatment are typically strait forward. Metastatic cancer can sometimes present as an inguinal hernia, but this presentation is often local metastasis. Case Presentation: Herein we describe the case of a 68-year-old man who presented with a 2-month history of an inguinal hernia. Intraoperatively, the hernia sac was found to contain a mass attached to the spermatic cord, which was later determined to be a metastatic lesion from a locally advanced proximal transverse colon adenocarcinoma. Conclusion: A spermatic cord mass can be a rare presentation of colon cancer metastasis. Colon cancer should be considered a rare but possible primary lesion when evaluating tumors of the spermatic cord.

Disease Control and Toxicity Outcomes after Stereotactic Ablative Radiation Therapy for Recurrent and/or Metastatic Cancers in Young-Adult and Pediatric Patients.

BACKGROUND: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. METHODS: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan-Meier estimates in R v4.2.3. RESULTS: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14-23 y) and the median follow-up was 18.1 months (IQR: 7.7-29.1). The median SABR dose was 30 Gy (IQR 25-35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). CONCLUSIONS: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field.

A new approach to combined proton-photon therapy for metastatic cancer patients.

Objective.Proton therapy is a limited resource and is typically not available to metastatic cancer patients. Combined proton-photon therapy (CPPT), where most fractions are delivered with photons and only few with protons, represents an approach to distribute proton resources over a larger patient population. In this study, we consider stereotactic radiotherapy of multiple brain or liver metastases, and develop an approach to optimally take advantage of a single proton fraction by optimizing the proton and photon dose contributions to each individual metastasis.Approach.CPPT treatments must balance two competing goals: (1) deliver a larger dose in the proton fractions to reduce integral dose, and (2) fractionate the dose in the normal tissue between metastases, which requires using the photon fractions. Such CPPT treatments are generated by simultaneously optimizing intensity modulated proton therapy (IMPT) and intensity modulated radiotherapy (IMRT) plans based on their cumulative biologically effective dose (BEDα/ß). The dose contributions of the proton and photon fractions to each individual metastasis are handled as additional optimization variables in the optimization problem. The method is demonstrated for two patients with 29 and 30 brain metastases, and two patients with 4 and 3 liver metastases.Main results.Optimized CPPT plans increase the proton dose contribution to most of the metastases, while using photons to fractionate the dose around metastases which are large or located close to critical structures. On average, the optimized CPPT plans reduce the mean brain BED2by 29% and the mean liver BED4by 42% compared to IMRT-only plans. Thereby, the CPPT plans approach the dosimetric quality of IMPT-only plans, for which the mean brain BED2and mean liver BED4are reduced by 28% and 58%, respectively, compared to IMRT-only plans.Significance.CPPT with optimized proton and photon dose contributions to individual metastases may benefit selected metastatic cancer patients without tying up major proton resources.

Surface-engineered erythrocyte membrane-camouflage fluorescent bioprobe for precision ovarian cancer surgery.

PURPOSE: Fluorescence imaging-guided surgery has been used in oncology. However, for tiny tumors, the current imaging probes are still difficult to achieve high-contrast imaging, leading to incomplete resection. In this study, we achieved precise surgical resection of tiny metastatic cancers by constructing an engineering erythrocyte membrane-camouflaged bioprobe (AR-M@HMSN@P). METHODS: AR-M@HMSN@P combined the properties of aggregation-induced emission luminogens (AIEgens) named PF3-PPh3 (P), with functional erythrocyte membrane modified by a modular peptide (AR). Interestingly, AR was composed of an asymmetric tripodal pentapeptide scaffold (GGKGG) with three appended modulars: KPSSPPEE (A6) peptide, RRRR (R4) peptide and cholesterol. To verify the specificity of the probe in vitro, SKOV3 cells with overexpression of CD44 were used as the positive group, and HLF cells with low expression of CD44 were devoted as the control group. The AR-M@HMSN@P fluorescence imaging was utilized to provide surgical guidance for the removal of micro-metastatic lesions. RESULTS: In vivo, the clearance of AR-M@HMSN@P by the immune system was reduced due to the natural properties inherited from erythrocytes. Meanwhile, the A6 peptide on AR-M@HMSN@P was able to specifically target CD44 on ovarian cancer cells, and the electrostatic attraction between the R4 peptide and the cell membrane enhanced the firmness of this targeting. Benefiting from these multiple effects, AR-M@HMSN@P achieved ultra-precise tumor imaging with a signal-to-noise ratio (SNR) of 15.2, making it possible to surgical resection of tumors < 1 mm by imaging guidance. CONCLUSION: We have successfully designed an engineered fluorescent imaging bioprobe (AR-M@HMSN@P), which can target CD44-overexpressing ovarian cancers for precise imaging and guide the resection of minor tumors. Notably, this work holds significant promise for developing biomimetic probes for clinical imaging-guided precision cancer surgery by exploiting their externally specified functional modifications.

DUX4 is a common driver of immune evasion and immunotherapy failure in metastatic cancers.

Cancer immune evasion contributes to checkpoint immunotherapy failure in many patients with metastatic cancers. The embryonic transcription factor DUX4 was recently characterized as a suppressor of interferon-γ signaling and antigen presentation that is aberrantly expressed in a small subset of primary tumors. Here, we report that DUX4 expression is a common feature of metastatic tumors, with ~10-50% of advanced bladder, breast, kidney, prostate, and skin cancers expressing DUX4. DUX4 expression is significantly associated with immune cell exclusion and decreased objective response to PD-L1 blockade in a large cohort of urothelial carcinoma patients. DUX4 expression is a significant predictor of survival even after accounting for tumor mutational burden and other molecular and clinical features in this cohort, with DUX4 expression associated with a median reduction in survival of over 1 year. Our data motivate future attempts to develop DUX4 as a biomarker and therapeutic target for checkpoint immunotherapy resistance.

Over time cancer patients can become resistant to traditional treatments such as chemotherapy and radiotherapy. In some cases, this can be counteracted by administering a new type of treatment called immune checkpoint inhibition which harnesses a patient's own immune system to eradicate the tumor. However, a significant proportion of cancers remain resistant, even when these immunotherapy drugs are used. This is potentially caused by tumors reactivating a gene called DUX4, which is briefly turned on in the early embryo shortly after fertilization, but suppressed in healthy adults. Activation of DUX4 during the early stages of cancer has been shown to remove the cell surface proteins the immune system uses to recognize tumors. However, it remained unclear whether DUX4 changes the response to immunotherapy in more advanced cancers which have begun to spread and metastasize to other parts of the body. To investigate, Pineda and Bradley analyzed publicly available sequencing data which revealed the genes turned on and off in patients with different types of cancer. The analysis showed that DUX4 is reactivated in approximately 10­50% of advanced bladder, breast, kidney, prostate and skin cancers. Next, Pineda and Bradley studied a cohort of patients with advanced bladder cancer who had been treated with immune checkpoint inhibitors. They found that patients with tumors in which DUX4 had been turned back on had shorter survival times than patients who had not reactivated the gene. These results suggest that the activity of DUX4 could be used to predict which patients with advanced bladder cancer may benefit from immune checkpoint inhibitors. In the future, this work could be extended to see if DUX4 could be used as a prognostic tool for other types of cancer. Future studies could also investigate if the DUX4 gene could be a therapeutic target for mitigating resistance to immunotherapy in metastatic cancers.

Testing the feasibility of mobile ecological momentary assessment for symptom burden and management among metastatic cancer patients.

Background: Individuals who have metastatic cancer experience substantial physical and psychological distress (e.g., pain, depression, anxiety) from their disease and its treatment compared to patients with less advanced disease. As the burden of symptoms varies over time, ecological momentary assessment (EMA) may be used to better understand patients' symptom trajectories, complimenting traditional longitudinal data collection methods. However, few have used EMA in patients with metastatic disease. The current study adds to the existing literature by exploring interrelated, common cancer-related symptoms of pain, anxiety, and depression and use of cannabis-based products, opioid medications, other (nonopioid) pain medications, and medications for anxiety or depression. Methods: An eight-day prospective observational feasibility study was conducted among 50 patients with metastatic cancer recruited from seven solid cancer clinics at The Ohio State University Comprehensive Cancer Center. Participants completed a week of interval-contingent mobile EMA, administered daily at 9 a.m., 3 p.m., and 8 p.m., and a comprehensive interviewer-administered questionnaire on Day 8. Participants were queried on their symptom burden and management strategies (i.e., use of medications and cannabis). We considered EMA to be feasible if a priori retention (80%) and adherence goals (75%) were met. Results: Seventy-nine percent of eligible patients contacted enrolled in the study (n = 50 of 63). Among those enrolled, 92% were retained through Day 8 and 80% completed >90% of EMAs, exceeding a priori objectives. Participants' average pain, anxiety, and depressive symptoms across the week of EMA ranged from 1.7 to 1.8 (1 to 5 scale). Symptoms varied little by day or time of administration. On Day 8, significant proportions of participants reported past-week use of medications and cannabis for symptom management. Conclusions: Participants exceeded a priori adherence and retention objectives, indicating that mobile EMA is feasible among metastatic cancer patients, addressing a gap in the existing literature and informing future research. Restricting eligibility to participants with a minimum cutoff of symptom burden may be warranted to increase observations of symptom variability and provide opportunities for future health interventions. Future research is needed to test the acceptability and quality of data over a longer study period in this patient population.

Early onset metastatic colorectal cancer in Australia.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP). METHODS: We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years). RESULTS: Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP. CONCLUSION: Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted.

Outcomes for breast cancer survivors with metastatic disease in a physical activity program for medically underserved cancer survivors.

PURPOSE: This study examined the effectiveness and feasibility of the Active Living After Cancer (ALAC) program for metastatic breast cancer (MBC) survivors. METHODS: ALAC is a 12-session community-based program to help cancer survivors improve their physical functioning and quality of life through increased physical activity. ALAC participants with MBC (stage IV) were compared to survivors with early-stage breast cancer (stages I and II). The International Physical Activity Questionnaire, Godin Leisure-Time Physical Activity, 30-second sit-to-stand test, and PROMIS Global Health were administered at baseline and follow-up. Program satisfaction and retention were assessed at week 12. Repeated-measures mixed models were used to compare changes in outcomes between survivors with early-stage breast cancer and MBC. RESULTS: A total of 585 women (59.3 y ± 10.6), most of whom were Hispanic (54%) or non-Hispanic Black (22%), were included (early stage, n = 538; MBC, n = 47). After the ALAC program, a significant increase in physical activity (P < 0.001), improved physical and mental health T-scores (P < 0.001), and more sit-to-stand repetitions (P < 0.001) were observed for both survivors with early-stage breast cancer and MBC. Women with MBC showed significantly lower physical health (P = 0.037) and physical function (P = 0.010) compared to early-stage at baseline. CONCLUSIONS: The ALAC program increased physical activity and improved health-related quality of life and physical function among breast cancer survivors with both early-stage and metastatic disease. IMPLICATIONS FOR CANCER SURVIVORS: This study emphasizes the importance of incorporating physical activity interventions like the ALAC program into the comprehensive care of cancer survivors, including those with metastatic disease.

Palliative Surgery for Patients with Gastroesophageal Junction or Gastric Cancer: A Report on Clinical Observational Outcomes.

BACKGROUND: Few studies have focused on palliative surgery in patients with advanced gastroesophageal junction (GEJ) or gastric cancer. We sought to evaluate clinical observational outcomes following palliative surgery in this population. PATIENTS AND METHODS: Patients with GEJ or gastric cancer who underwent palliative surgery (1/2010-11/2022) were identified. The primary outcomes were symptom improvement, ability to tolerate an oral diet, discharge to home, 30 "good days" without hospitalization, and receipt of systemic treatment. Postoperative outcomes and survival were secondarily evaluated. RESULTS: Among 93 patients, the median age was 59 (IQR 47-68) years, and the median Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was 1 (range 0-3). The most frequent indication for palliative surgery was primary tumor obstruction [75 (81%) patients]. The most common procedures were feeding tube placement in 60 (65%) and intestinal bypass in 15 (16%) patients. A total of 75 (81%) patients experienced symptom improvement. Of these, 19 (25%) developed recurrent and 49 (65%) developed new symptoms. ECOG-PS was significantly associated with symptom-free time. Among those who underwent a bypass, resection, or ostomy creation for malignant obstruction, 16 (80%) tolerated an oral diet. Postoperatively, 87 (94%) were discharged home, 72 (77%) had 30 good days, and 64 (69%) received systemic treatment. Postoperative complications occurred in 35 (38%) patients, and 7 (8%) died within 30 days. The median survival time was 7.7 (95% CI 6.4-10.40) months. CONCLUSIONS: Patients with incurable GEJ or gastric cancer can benefit from palliative surgery. Prognosis and performance status should inform goals-of-care discussions and patient selection for surgical palliation.

Trastuzumab deruxtecan in previously treated HER2-positive metastatic or unresectable breast cancer: Real-life data from the temporary use authorization program in France.

BACKGROUND: Early access program (formerly cohort Temporary Authorization for Use) was granted for trastuzumab deruxtecan (T-DXd) in France based on DESTINY-Breast01 trial which demonstrated its efficacy and safety in HER2-positive metastatic/unresectable breast cancer after ≥2 anti-HER2-based regimens received at metastatic stage. METHODS: This multicenter real-world early access program included HER2-positive metastatic/unresectable breast patients pretreated with at least two lines of anti-HER2 regimens who received T-DXd 5.4 mg/kg intravenously in monotherapy every 3 weeks. RESULTS: Four hundred and fifty-nine patients (median age, 58 years; hormone receptor-positive, 67%; brain metastases, 28.1%) received T-DXd. Before inclusion, 81.7% of patients had radiation therapy and 76.5% had undergone surgery. Median number of prior metastatic treatment lines was four (range, 2-22); 99.8% patients had received trastuzumab, 94.8% trastuzumab emtansine and 79.3% pertuzumab. Follow-up was performed from September 30, 2020 to March 30, 2021; when the early access program stopped, the median duration of T-DXd treatment was 3.4 (range, 0-7.8) months. In 160 patients with available tumor assessment, objective response rate was 56.7% and 12.1% had progression. In 57 patients with available brain tumor assessment, complete or partial intracranial response was reported for 35.7% patients and 5.4% had progression. A total of 17 (3.7%) patients with interstitial lung disease (ILD) was reported with no cases of ILD-related death. CONCLUSIONS: In this early access program in patients with heavily pretreated HER2-positive metastatic/unresectable breast cancer, T-DXd had antitumor activity with a similar response to that reported in previous clinical studies. T-DXd was well tolerated and no new safety signals were observed.

Gastric Ulcer With Yttrium-90 Microsphere Selective Internal Radiation Therapy.

Radioembolization with yttrium-90 (Y90) is a recent oncological interventional radiology technique used to treat hepatocellular carcinoma and metastatic colon cancer to the liver. Although Y90 selective internal radiation therapy (Y90-SIRT) is considered a safe and effective treatment, with increasing use, hepatic and extrahepatic complications have been reported. Here, we present a case of upper gastrointestinal bleeding caused by gastric ulceration associated with radioembolization from Y90-SIRT, as confirmed by histological findings. Unlike dyspeptic ulcers, radioembolization ulcers originate on the serosal surface, predisposing patients to adhesions, bowel obstruction, or perforation, as well as gastrointestinal bleeding.

"It gave me a sense of achievement and a sense of purpose"-a qualitative study of patient experiences of a virtually supervised exercise program for adults with advanced cancer and cachexia.

People with advanced cancer and cachexia experience significant body weight loss, adversely impacting physical function and quality of life (QOL). Effective, evidence-based treatments for cancer cachexia are lacking, leaving patients with unmet needs. Exercise holds promise to improve patient QOL. However, information on patients' experiences of exercise, including their ability to cope with structured exercise, is limited. PURPOSE: To explore patient experiences completing a structured, supervised exercise program for people with cachexia due to advanced cancer. METHODS: Semi-structured interviews were conducted with participants enrolled in a phase II feasibility, randomized controlled trial to explore their experiences of an 8-week virtually supervised exercise program delivered via videoconference technology. Interviews were analysed using reflexive thematic analysis. RESULTS: Seventeen participants completed interviews (female n = 9, 53%). Main interview themes included the following: (1) Deciding to exercise involves balancing concerns and expectations, (2) the exercise program is a positive experience, and (3) moving forward after the exercise program. While some participants initially held doubts about their physical capabilities and exercise safety, most wanted to exercise to enhance their wellbeing. Participants described the exercise program as a positive experience, offering diverse benefits. Some would have preferred in-person exercise, but all agreed the virtual format increased convenience. Participants emphasized the need to recommend the program to others in similar circumstances. They underscored the necessity and desire for ongoing support to sustain their new exercise habits. CONCLUSION: Based on patient experiences, virtually supervised exercise programming appears to be feasible and meaningful to people with advanced cancer and cachexia.

Estimating scenarios for survival time in patients with advanced melanoma receiving immunotherapy and targeted therapy.

BACKGROUND: We aim to provide survival scenario estimates for patients with advanced melanoma starting targeted therapies and immunotherapies. MATERIALS AND METHODS: We sought randomized trials of targeted therapies and immunotherapies for advanced melanoma and recorded the following percentiles (represented survival scenario) from each overall survival (OS) curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical), and 10th (best-case). We tested whether these scenarios can be estimated for each OS curve by multiplying its median by 4 multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case). RESULTS: We identified 15 trials with 8025 patients. For first-line combination targeted therapy treatment groups, the median (interquartile range, IQR) in months for each percentile was: 90th, 6.2 (6.0-6.5); 75th, 11.3 (11.3-11.4); and median, 24.4 (23.5-25.3). For the first-line combination immunotherapy treatment group, the percentiles in months were: 90th, 3.9 (2.8-4.5); 75th, 13.4 (10.1-15.4), median 73 (not applicable). In targeted therapy groups, simple multiples of the median OS were accurate for estimating the 90th percentile in 80%; 75th percentile in 40%; 25th percentile in 100%. In immunotherapy groups, these multiples were accurate at 0% for the 90th percentile, and 43% for the 75th percentile. The 90th percentile (worst-case scenario) was better estimated as 1/6× median OS, and the 75th percentile (lower-typical) as 1/3× median OS. CONCLUSIONS: Simple multiples of the median OS are a useful framework to estimate scenarios for survival for patients receiving targeted therapies, not immunotherapy. Longer follow-up is required to estimate upper-typical and best-case scenarios.