Curative-intent Treatment Research Articles

A Prospective Trial of Biomarker-Guided Surveillance for HPV-Positive Oropharynx Cancer Using Plasma Tumor Tissue–Modified Viral HPV DNA

Abstract Purpose: Observational studies suggest circulating tumor human papillomavirus (HPV) DNA may facilitate early detection of recurrent HPV-positive oropharynx cancer. We prospectively investigated whether biomarker-guided surveillance detects recurrence earlier than the standard-of-care methods. Patients and Methods: We enrolled patients evaluated for HPV-positive oropharynx cancer at a single center from November, 2020, to April, 2023, undergoing curative-intent treatment in a single-arm cohort study. Pretreatment plasma and/or tumor tissue were tested for tumor tissue–modified viral (TTMV) HPV DNA from HPV subtypes 16/18/31/33/35 using a droplet digital PCR–based commercial assay. Posttreatment plasma TTMV was assessed periodically. Detectable/indeterminate tests prompted imaging. The primary outcome was the proportion of recurrences first detected by TTMV. Results: Median follow-up was 23 months, with median six posttreatment TTMV tests for 155 subjects. Fifteen subjects (9%) experienced recurrence. Among these, six [40%, 95% confidence interval (CI) = 16%–68%] were “early true-positives,” for whom TTMV detection predated and prompted the imaging and clinical workup that diagnosed recurrence (median lead time = 132 days; range = 47–280). Another five subjects (33%) were “confirmatory true-positives,” for whom detectable TTMV confirmed suspicious standard-of-care imaging findings. Finally, four subjects (27%) with recurrence had undetectable TTMV at diagnosis (“false-negatives”). False-negatives had low or undetectable pretreatment TTMV, and 2/4 had non-HPV16 genotypes. Finally, three subjects had prolonged detectable TTMV without disease (“false-positives”); all had immunologic comorbidities. Overall, the sensitivity of TTMV for recurrence was 73% (95% CI = 45%–92%). Among 117 subjects with HPV16 and detectable pretreatment TTMV, sensitivity was higher (91%, 95% CI = 59%–100%). Conclusions: TTMV-guided surveillance facilitates early detection of many HPV-positive oropharynx cancer recurrences, with the highest sensitivity for HPV16 and detectable pretreatment TTMV. Clinical implementation should be carefully informed by the limitations described in this study.

AS YOUNG AS YOU FEEL? TRACKING SUBJECTIVE AGE AND PHYSICAL WELL-BEING BEFORE A LUNG CANCER SCAN

Abstract Research has not yet considered how cancer-related events trigger poor quality of life. Here, researchers examined whether the discrepancy between felt and chronological age was related to physical well-being, and if these fluctuated as patients with lung cancer approached a triggering event – repeated CT scans. 25 patients treated with curative intent treatment for lung cancer were recruited within 6 months of their upcoming CT scan. Patients were predominantly white (80%; Black: 12%), women (96%), between 43 and 78 years old (M = 62.33, SD = 8.10). Baseline surveys collected age, and repeated monthly surveys gathered physical well-being and felt age every 30 days until one’s scan. Following a monthly response rate of 100% (59 of 59 received), researchers calculated proportional discrepancy felt age scores by subtracting chronological age from felt age and dividing by chronological age. Using this score, researchers investigated the monthly relationship between age discrepancy and physical well-being. Results showed that on months when patients felt closer to, or older than, their chronological age they reported increases in physical well-being (γ10 = 1.75, t = 2.13, p =.04). The present model accounted for 33% of the within-person, and 39% of the between-person variance of physical well-being. In contrast to studies in non-clinical populations, results showed that feeling older was associated with better physical well-being in the months prior to a CT scan. Qualitative interviews could identify themes in coping with repeated scans that may mitigate the effects cancer treatment can have on physical well-being.

Safety and Toxicity of Iopofosine I 131 (CLR 131) with External Beam Radiation Therapy in Recurrent or Metastatic Head and Neck Cancer: Results of a Phase 1 Single-Centre, Open-Label, Single-Arm, Dose Escalation and Dose Expansion Study

Re-irradiation of recurrent head and neck cancer (HNC) is often limited by tumour adherence to critical structures and/or radiation tolerance of critical normal tissues. Iopofosine I 131 (CLR 131) is a targeted small molecular phospholipid ether (PLE) drug conjugate that delivers iodine-131 selectively to tumour cells. We conducted a phase 1, single-centre, open-label study to determine whether CLR 131 given with reduced dose of external beam radiation therapy (EBRT) would be tolerable and feasible. All participants received previous curative intent treatment with radiotherapy as primary or adjuvant treatment. Eligible participants demonstrated uptake of CLR 131 as indicated via single photon emission CT/CT (SPECT/CT) imaging following CLR 131 test dose. Participants received two therapeutic doses of CLR 131 (days 1 and 8) with SPECT/CT imaging performed to quantitate the biodistribution of CLR 131. Participants subsequently received EBRT to achieve the designated radiation dose (60-70Gy). The primary endpoint was safety. This trial was registered with ClinicalTrials.gov, NCT04105543, and enrolment and follow-up are complete. Twelve participants completed treatment with CLR 131 and EBRT. Eight participants experienced grade 4 non-DLT haematologic toxicities (2 anaemia, 8 leukopenia, 5 thrombocytopenia) at least probably attributed to CLR 131, consistent with the expected toxicity profile. Haematologic toxicities occurred during weeks 6-8 from the first dose of CLR 131 and resolved within three weeks without sequelae. There were no treatment-related grade 3-4 non-haematologic toxicities. CLR 131 in combination with EBRT did not confer any safety concerns, and was tolerable in participants with recurrent/metastatic HNC. Myelosuppression was consistent with the known toxicity profile of CLR131. National Institutes of HealthP50 DE026787, National Cancer InstituteP30 CA014520, National Institutes of Health1UL1TR002373, Cellectar, NCT04105543.

Palliative radiation therapy for locally advanced breast cancer.

Globally, breast cancer is the most commonly diagnosed cancer in women. Locally advanced breast cancers (LABCs) may necessitate palliative radiation therapy (RT) due to the severity of the patients' symptoms, inoperability, or other reasons precluding curative-intent treatment such as poor performance status and patient comorbidities. This review aims to discuss current evidence on palliative RT in LABC. Advanced targeted RT techniques have led to improvements in local control with reduced treatment-related toxicities. Emerging short-course palliative RT prescriptions offer feasible options that avoid delay in systemic therapy. Additionally, recent studies also highlight approaches for integrating palliative RT with systemic therapies. Palliative RT plays a vital role in managing symptoms and enhancing quality of life for LABC patients. However, there is currently no consensus on the optimal prescriptions for palliative RT in these patients. Standardized reporting of palliative RT studies is needed for robust comparison of efficacy and toxicity between various treatment regimens. Furthermore, future research on the optimal integration of RT with novel systemic agents is needed.

The influence of the introduction of a nationwide screening program for colorectal cancer on the proportion of curative intent treatment in patients with isolated liver, peritoneal or lung metastases

The influence of the introduction of a nationwide screening program for colorectal cancer on the proportion of curative intent treatment in patients with isolated liver, peritoneal or lung metastases

Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Final Results of the ORATOR Randomized Trial.

Radiotherapy (RT) and transoral robotic surgery (TORS) are both curative-intent treatment options for oropharyngeal squamous cell carcinoma (OPSCC). Herein, we report the final outcomes of the ORATOR trial comparing these modalities, 5 years after enrollment completion. We randomly assigned 68 patients with T1-2N0-2 OPSCC to RT (with chemotherapy if node-positive) versus TORS plus neck dissection (± adjuvant RT/chemoradiation). The primary end point was swallowing quality of life (QOL) assessed with the MD Anderson Dysphagia Inventory (MDADI). Secondary end points included overall and progression-free survival (OS, PFS), adverse events (AEs), and other QOL metrics. The primary end point has been previously reported (Nichols 2019). In this report, the median follow-up was 5.1 years (IQR, 5.0-5.3 years). MDADI total scores converged by 5 years and were not significantly different across the follow-up period (P = .11). EORTC QLQ-C30 and H&N35 scores demonstrated differing profiles, including worse dry mouth in the RT arm (P = .032) and worse pain in the TORS arm (P = .002). Grade 2-5 AE rates did not differ between arms (91% [n = 31] v 97% [n = 33] respectively, P = .61), with more neutropenia and hearing loss in the RT arm, and more dysphagia and other pain in the TORS arm based on grades 2-5 (all P < .05). There were no differences in OS or PFS. In conclusion, toxicity and QOL profiles differ in some domains between RT and TORS, but oncologic outcomes were excellent in both arms. Choice of treatment should remain a shared decision between the patient and their providers.

Early Palliative Care Following Aborted Cancer Surgery: Results of a Prospective Feasibility Trial.

Although resection is generally necessary for curative-intent treatment of most solid organ cancers, surgery is occasionally aborted due to intraoperative findings. Following aborted cancer surgery, patients have unique care needs that specialized palliative care (PC) providers may be best equipped to manage. We hypothesized that early ambulatory PC referral following aborted cancer surgery would be feasible and acceptable. This single-institution prospective clinical trial enrolled adult patients with gastrointestinal or hepatopancreatobiliary cancer with no prior PC exposure who had curative-intent oncologic surgery that was unexpectedly aborted. The primary endpoint was the completion of an ambulatory PC consultation within 30 days of enrollment. Secondary outcomes included changes in standardized measures of quality-of-life (QOL) and anxiety/depression during the 3-month follow-up. Among 25 enrolled participants, the mean age was 65.3 ± 9.9 years, 68% were male, and 88% were White. The most common types of cancers were pancreatic (44%), hepatobiliary (20%), and colorectal (12%); reasons for aborting surgery were occult metastatic disease (52%) and local unresectability (36%). Only 13 of 25 (52%) met the primary endpoint of ambulatory PC within 30 days, less than the prespecified threshold of 70%. Overall, 16 (64%) patients completed ambulatory PC consultation a mean of 29.2 ± 15.8 days after enrollment. Of the 9 (36%) who did not, reasons included patient preference (n = 4), withdrawal from study (n = 1), lost to follow-up (n = 1), scheduling conflict (n = 1), and required inpatient PC before discharge (n = 2). Anxiety (4.94 ± 3.56 vs 3.35 ± 2.60, P = 0.06), depression (4.18 ± 4.02 vs 4.76 ± 3.44, P = 0.49), and QOL (82.44 ± 11.41 vs 82.03 ± 15.37, P = 0.92) scores did not significantly differ at 3-month follow-up compared to baseline. Barriers to early ambulatory palliative care consultation exist after aborted cancer surgery. Given the unique and complex care needs of this patient population, additional research is needed to optimize supportive care strategies.

OGC SO03 - Impact of recent European consensus guidelines on Oligometastic Disease (OMD) and potential case load of Oesophagogastric cancer resections

Abstract Background To evaluate the impact of recently devised oligometastatic disease (OMD) criteria as per the European consensus guidelines on the eligibility of Oesophagogastric (OG) cancer patients for curative treatment. Method A retrospective analysis was conducted on OG cancer cases discussed at multidisciplinary team (MDT) meetings at a tertiary university hospital from January 2018 to December 2023. Inclusion criteria included T2-T4a adenocarcinomas, T2-T4b squamous cell carcinomas, small cell carcinoma and adeno-squamous carcinomas that were classified as M1 disease. Exclusion criteria were T4b adenocarcinomas, M1 peritoneal disease, non-adeno/ squamous carcinoma histology, M1 peritoneal cytology, and head and neck squamous cell carcinomas proximal to the thoracic inlet. Data on patient demographics, T stage, histology, and metastatic sites were analysed to identify those meeting the oligometastatic disease criteria. Results 483 of 696 were diagnosed as M1 disease. OMD was found in 59 cases (12.2%), with a median age of 72 years (43 males, 16 females). T stage distribution: 3 T2, 36 T3, 20 T4. Histology: 39 adenocarcinomas, 19 squamous cell carcinomas, 1 small cell carcinoma. Metastatic sites: non-regional lymph nodes (77.9%), liver (13.6%), lung (5.1%), bone (1.7%), adrenal (1.7%) Location of Lymph Node Involvement: 1Para-aortic11 (23.9%)2Right supra-clavicular7 (15.2%)3Porto-caval6 (13.0%)4Retro-crural5 (10.9%)5Upper mediastinal5 (10.9%)6Left Supraclavicular5 (10.9%)7Coeliac4 (8.6%)8SMA3 (6.6%) Conclusion Our data would suggest that 12.2% of patients discussed in the MDT may potentially be candidates for a curative intent treatment pathway. Although the long-term outcomes remain unclear, this approach may define a subgroup of patients who may benefit from curative intent treatment with the highest site being para-aortic nodes.

A06 - OGC LAsting Symptoms after Oesophageal Resectional Surgery (LASORS): Multicentre validation cohort study

Abstract Background Patients are living longer with the long-term morbidity of oncological and surgical therapies as oesophageal cancer outcomes improve. Existing symptomatology and quality of life tools are cumbersome and moreover not designed for the post-treatment survivorship setting. The LASER study identified six key symptoms thought to predict poor health-related quality of life. The current study aimed to validate this six-symptom LAsting Symptoms after Oesophageal Resection (LASOR) clinical tool, and assess its clinical utility. Method Between 2015 and 2019, patients from UK centres who underwent curative-intent oesophageal cancer treatment, and were disease-free at least one year postoperatively, were asked to complete LASOR, EORTC QLQ-C30 and QLQ-OG25 questionnaires. LASOR symptoms (low mood, reduced energy, thoracotomy pain, heartburn, diarrhoea, and bloating after eating) were correlated with EORTC HRQOL scores. Multivariable regression analysis identified symptoms associated with poor HRQoL. Receiver operating characteristic curve analysis was used to validate the LASOR tool. Results 263 patients, spanning a combination of surgical approaches (two-stage, three-stage, left thoracoabdominal, transhiatal), techniques (open, minimally invasive, hybrid), and disease stage, completed the questionnaires. Four of the six LASOR symptoms were associated with poor HRQoL: reduced energy (OR 2.13; 95% CI 1.20-2.87), low mood (OR 1.86; 95% CI 1.4503.12), diarrhoea (OR 1.48; 95% CI 1.06-2.05), and bloating after eating (OR 1.35; 95% CI 1.03-1.77). The LASOR tool produced an area under the curve of 0.85. Conclusion The six-symptom LASOR tool generated a reliable model for identification of patients with a poor HRQOL, with an overall diagnostic accuracy of over 80%. This is the first clinical symptom and quality of life tool to be validated in esophageal cancer patients post-curative treatment. The LASOR tool is straightforward to administer and acceptable to patients. Clinical utility lies both in identifying patients at risk of poor HRQoL and in planning survivorship services.

Features of late local failure of early‑stage non‑small cell lung cancer treated with stereotactic body radiotherapy.

Local failure of non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) often occurs within 2 years and delayed local failure is uncommon. In the present study, features of late local failure (LLF; >2 years after SBRT) after SBRT were investigated and compared with those of early local failure (ELF; ≤2 years after SBRT) to explore whether these two local recurrence features have different prognostic implications. Patients who underwent SBRT for stage I-IIA NSCLC between July 2006 and March 2014 were retrospectively reviewed. Overall, 173 patients underwent SBRT for NSCLC. The median follow-up times after SBRT were 50 and 31 months for survival and computed tomography (CT) follow-up, respectively. LLF and ELF occurred in 7 and 13 patients, respectively. The median times to LLF and ELF were 42 months (range, 31-61 months) and 13 months (range, 4-16 months), respectively. Local-only failure occurred in 14% (1/7) of LLF cases and 77% (10/13) of ELF cases, which was significantly different (Fisher's exact test, P=0.02). Curative-intent salvage treatment was impossible in all of the LLF cases and 69% (9/13) of the ELF cases, which was significantly different (Fisher's exact test, P<0.01). The median survival times after local failure were 9 and 25 months for patients with LLF and ELF, respectively. Additionally, the 1-year overall survival rates after local failure were 29 and 83% in the LLF and ELF groups, respectively, which was significantly different (log-rank test, P<0.01 at 1-year). In summary, the prognosis after LLF was significantly unfavorable compared with after ELF. Curative-intent salvage treatment is often difficult for LLF due to metastases. Therefore, it seems reasonable to decrease the frequency of follow-up CT for detecting tumor recurrence after the first 2 years post-SBRT.

The out-of-pocket cost of breast cancer care in Nigeria: A prospective analysis

BackgroundMost patients pay out-of-pocket for cancer care in Nigeria, which can result in a catastrophic health care expenditure (CHE). There is a paucity of economic data on the cost of care and the impact this may have on the household. This study provides a prospective analysis of direct and indirect out-of-pocket costs for breast cancer care at a single tertiary care institution in South West Nigeria. MethodsConsecutive patients undergoing curative intent treatment for a new diagnosis of breast cancer between August 2019 and September 2022 were approached for enrollment. A novel questionnaire was delivered to patients during hospital admission and again during six-month follow-up. Patients self-reported annual household income, capacity-to-pay, and all direct and indirect expenditures associated with access care. A CHE was defined using three commonly used definitions, including total healthcare expenditure that exceeds 40 % of a household's capacity-to-pay, or exceeds the proportion of annual income set at thresholds of 10 % and 25 %. ResultsData were collected from 71 eligible patients with a mean age of 49.5 years (SD 11.26). Sixty-six percent (47/71, 66.2 %) of patients had ≥ Stage III disease at presentation, and 95.8 % received systemic chemotherapy. Only 23.9 % received adjuvant radiotherapy. The mean annual capacity-to-pay for the cohort was $2866.93 (SD $2749.74). The mean cost of care was $5192.77 (SD $4567.71). Out of the 71 patients enrolled in the study, between 56 (78.9 %) and 71 (100 %) experienced a CHE, depending on the included costs (direct +/- indirect) and threshold used. Sixty-six percent of patients had no form of health insurance. ConclusionsOver 70 % of breast cancer patients at a tertiary care facility in Nigeria experience a CHE because of out-of-pocket costs associated with accessing care. Policy summaryA more effective and accessible health insurance mechanism is required in Nigeria to protect women with breast cancer from the cost of cancer care.

Second Events After Curative-Intent Treatment for Lip Cancer: Navigating the Path of Follow-Up Care.

We aimed to investigate the pattern, risk, and treatment of subsequent events after curative-intent treatment of lip cancer. This retrospective cohort study included 313 patients treated for lip cancer from 2011 to 2021 in a tertiary oncological center. After a median follow-up time of 29.16 months, 145 (46.32%) patients presented with second primary tumors, 93% of which were skin carcinomas. Locoregional recurrence occurred in 7.9% of cases, with 2.5% with nodal recurrence. The 1-, 5-, and 10-year cumulative second primary tumor probabilities were 32.8%, 60.92%, and 70.92%, respectively. A higher risk was observed in elderly patients and basal cell carcinoma cases located on the cutaneous surface of the upper lip. Regional metastasis but not second primary tumors negatively impacted survival. Our study helps fill a literature gap, structuring specific recommendations regarding evaluations and follow-up protocols for patients with lip cancer. Since cutaneous second primary tumors were the most common second event, standard skin examination is key. Age and histology were significant predictors for second primary tumors. For cases of locally advanced lip squamous cell carcinoma, standard guidelines for head and neck cancer must be followed.

A comprehensive approach to defining the cutoff value of oligometastasis in head and neck squamous cell carcinoma.

Patients with limited distant metastatic disease, also known as oligometastasis, show better survival rates than polymetastatic patients, and may be amenable for curative-intent treatment. The definition of oligometastasis, however, is unknown, and no quantitative analyses on the cutoff value for oligometastasis have been performed before. This study aims to derive specific threshold values for the number of metastases and affected locations that defines oligometastatic disease in head and neck squamous cell carcinoma. A retrospective cohort study was conducted including all patients diagnosed with distant metastases between 2006 and 2021. For each patient, the number of distant metastases and affected locations was recorded on the basis of the available imaging at the time of diagnosis. Cox regression analyses and a machine-learning k-means algorithm were used to determine threshold values. A total of 384 patients untreated for their metastatic foci were analyzed. Most patients (n=207; 53.9%) had metastasis to one anatomic location, followed by metastases in two anatomic locations (n=62; 16.1%). The majority of patients had ≥9 metastatic foci (n=174; 45.3%), followed by one focus (n=74; 19.3%) and two foci (n=32; 8.3%). Cox regression and machine-learning k-means models showed that although the number of metastases did not predict survival, the number of affected locations did significantly (p<.001), by identifying a threshold of two locations. Contrary to the prevalent dogma, the definition of oligometastasis should not be defined by the number of metastases but rather by the number of affected locations, with a maximum number of affected locations set at two.

Curative-intent surgery for solitary bone metastasis from extremity and trunk wall sarcoma: What are the outcomes and complications?

IntroductionApproximately 40–50 % of sarcoma patients will develop lung metastasis, but only 10 % will develop bone metastasis. The survival benefit of surgery for solitary bone metastasis remains unclear. MethodsFrom 1987 to 2019, 47 patients who underwent curative-intent treatment for localized bone or soft tissue sarcoma in the extremities or trunk wall developed solitary bone metastases as the first distant recurrence. Of them, 51 % (24/47) received curative-intent metastasectomy. We compared the clinicopathologic characteristics of the metastasectomy versus non-metastasectomy patients and evaluated the prognostic impact of solitary bone metastasectomy. The primary outcome measure was disease-specific survival (DSS) after developing solitary bone metastasis. ResultsThe post-metastasis DSS was worse with larger primary tumour size (HR 1.09; 95 % CI 1.02–1.16; p = 0.01) and bone metastasis in the pelvis or spine versus other bones (HR 3.79, 95 % CI 1.46–9.87; p = 0.01), and better with curative-intent surgery for the solitary bone metastasis (HR 0.14; 95 % CI 0.06–0.34; p < 0.001). The median DSS was 43 (95 % CI, 24–69) months for the metastasectomy group vs. 13 (95 % CI, 7–19) months for the non-metastasectomy group (p < 0.001). The metastasectomy group had fewer patients with metastasis in the spine or pelvis and longer metastasis-free interval. In the multivariate analysis, curative-intent surgery for solitary bone metastasis was associated with better survival (HR 0.21; 95 % CI 0.08–0.53; p = 0.001). ConclusionsCurative-intent surgery for solitary bone metastasis from sarcoma is associated with a better prognosis and is a reasonable treatment strategy whenever feasible.

Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory Study

IntroductionMolecular residual disease detected by circulating tumor DNA (ctDNA) has been reported to be predictive of patients’ outcomes in various types of cancers after curative intent treatment. Nevertheless, additional detailed information regarding the association of longitudinal ctDNA detection with long-term follow-up in lung cancer is needed. Here, we report on a cohort of patients with NSCLC who underwent definitive surgery and ctDNA analysis in the pre-operative, adjuvant, and surveillance settings. MethodPlasma samples were collected from 46 patients with clinical stage II-III NSCLC before surgery (N = 46), after surgery (N = 45), and every six months until two years thereafter (N = 78). A clinically validated, personalized, tumor-informed 16-plex polymerase chain reaction–next-generation sequencing assay was used for the detection and quantification of ctDNA in retrospectively analyzed plasma samples. ResultsCirculating tumor DNA was detected in the first postoperative (within 51 days after surgery) plasma samples in 13% (6/45) of patients (landmark analysis). All of them had disease recurrence within a median of 9.1 months. These patients had shorter recurrence-free and overall survivals than those without detectable ctDNA at a landmark time point (p < 0.01) and in multivariate analyses (p < 0.03). Longitudinally (considering all postoperative follow-up time points), ctDNA was detected in 13 patients, all of whom experienced disease recurrence (positive predictive value = 100%). Three patients who had central nervous system–only metastases did not have detectable ctDNA. ConclusionsThe presence of ctDNA post-surgery or during surveillance identifies patients with NSCLC at high risk of recurrence. Serial testing is important to detect disease recurrence earlier (lead-time: 3.2 months).

Cellular therapy in older adults with relapsed/refractory diffuse large B-cell lymphoma.

Relapsed/Refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with poor prognosis and limited therapeutic options. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (autoHCT) was historically the curative-intent treatment for patients who demonstrated chemosensitivity to salvage therapy. However, a significant portion of patients do not make it autoHCT due to disease progression or overall fitness and eligibility. This is of particular concern in the older adult population. In recent years, significant advances in cellular therapies including chimeric antigen receptor (CAR) T-cells and bispecific antibodies, in addition to improvement in autoHCT tolerability, have allowed for additional treatment options for patients with R/R DLBCL. These novel therapies offer the potential for durable remissions and cure, and should be considered in older patients. We present a review focused on the safety and efficacy of cellular therapies in the older adult population with R/R DLBCL.

Evaluating the Impact of Age and G8 Assessment on Definitive Treatment Strategies in Elderly Patients with Local Advanced Esophageal Carcinoma

Introduction: While chemoradiotherapy (CRT) is commonly employed as a curative approach for esophageal cancer, administering standard CRT to elderly patients often presents challenges in practical settings. The objective of this study was to compare treatment tolerance and survival outcomes between younger and elderly patients (aged ≥65 years) diagnosed with locally advanced esophageal cancer receiving curative-intent treatment. Additionally, it aimed to assess the impact of the Geriatric-8 Health Status Screening Tool (G8 score) on treatment decisions in elderly patients. Methods: Ninety-seven patients treated with neoadjuvant or definitive CRT for locally advanced esophageal cancer were retrospectively evaluated at two centers from 2013 to 2023. We divided the patients by age (<65 and ≥65 years) and assessed their demographic, clinical, and treatment data, including pre- and post-treatment G8 scores. Radiotherapy (RT) was administered at a median dose of 50.4 Gy (45–66 Gy). Planned concurrent chemotherapy was completed in 73 (75.3%) of the patients. Results: In the comparative study of 97 esophageal cancer patients, 48 geriatric (aged ≥65 years) and 49 younger individuals were followed up for a median of 20 and 21 months, respectively. No significant statistical differences were noted between the groups concerning baseline and treatment characteristics. Surgical intervention rates were comparable, with 22.9% of geriatric and 36.7% of young patients undergoing surgery (p = 0.184). There were no significant differences in pathological complete response, local recurrence, distant metastasis, progression, or death rates. The median progression-free survival (PFS) for geriatric and younger patients was 31 months (95% CI, 13.6–48.4) and 19 months (95% CI, 0–39.4), respectively (p = 0.832). The median overall survival (OS) was 38 months (95% CI, 23.8–52.2) in geriatric patients, while it was not reached in younger patients (p = 0.745). There was no significant difference between the two groups. The pretreatment and post-treatment G8 values of the geriatric patients were 9.25 (6–13.5) and 9.5 (6–14), respectively. Patients with increased G8 scores were found to have significantly higher PFS (median 85 months vs. 11 months, p = 0.001) and OS (median 85 months vs. 14 months, p = 0.001) compared to those with unchanged or decreased G8 scores. Conclusion: Age alone should not be the determining factor in the treatment decision of elderly patients diagnosed with locally advanced esophageal cancer. Moreover, CRT could be safely performed even in patients with low G8 scores, and although the G8 score may not directly influence treatment decision, its enhancement during the treatment process holds significant prognostic value.

Prognostic value of PSMA PET in predicting long-term biochemical control following curative intent treatment for prostate cancer.

The aim of this study is to investigate the prognostic value of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) metrics in predicting long-term biochemical failure-free survival (BFFS) following curative intent treatment for prostate cancer. We completed a prospective study that followed men who had PSMA PET for staging of newly diagnosed prostate cancer between 2015 and 2017 who went on to have curative intent treatment with radiotherapy (RT) or radical prostatectomy (RP). PSMA PET CT imaging was reported and the intraprostatic maximum standardised uptake value (SUVmax) was recorded. The primary outcome was BFFS. Statistical analysis included descriptive statistics, Cox proportional hazards (PH) models, Kaplan-Meier survival analysis and a regression tree structured method. A total of 183 men were included in the analysis with a median age of 66 years and the majority of patients (55.2%) had ISUP grade 1-3 disease. All patients had PSMA PET staging prior to curative intent treatment with RP (66.1%) or external beam radiotherapy (33.9%). PSMA-avid pelvic nodes were present in 26 patients but were not associated with worse biochemical control. A PSMA SUVmax of the prostate primary greater than the median (>5.6) was associated with a lower BFFS (HR: 4.4, 95% CI 1.42-3.72, P = 0.01). A multivariate Cox model incorporating initial biopsy grade, age and PSMA SUVmax showed that PSMA SUVmax was an independent predictor of BFFS. The RT-structured method identified an optimal threshold of 6.8 for PSMA SUVmax, above which patients with ISUP 1-3 disease had a significantly worse BFFS. PSMA SUVmax is a strong predictor of BFFS in patients with non-metastatic prostate cancer who underwent curative intent treatment. Patients with low-risk disease on biopsy (ISUP 1-3) but high PSMA SUVmax may have biochemical failure risk analogous to higher-risk disease (ISUP 4-5). These findings allow for further risk stratification and prognosis of patients with newly diagnosed prostate cancer planned for definitive treatment.

Biliary drainage in palliative and curative intent European patients with hilar cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis

Background and aimsRelief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy – including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented.Patients and methodsWe performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients.Results56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) < 2 mg/dl: 66.1% vs. 27.8%, p = < 0.001, > 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia.ConclusionsBiliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients.

Variability in treatment approaches, outcomes, and recurrence patterns after curative intent treatment for primary retroperitoneal sarcomas in Latin America: A report on 333 patients from LATAMSARC collaborative working group

Background and objectiveRetroperitoneal sarcomas (RPS) are rare tumors with several well-defined histologic subtypes. This study aimed to assess the epidemiology, treatment patterns, and outcomes of patients with retroperitoneal sarcoma in Latin America and analyze patterns of recurrence and treatment variations in a large population of patients treated at reference centers. MethodsThis retrospective descriptive study utilized an electronic database of medical records from LATAMSARC (a group studying sarcomas consisting of different centers in various countries in Latin America, including Argentina, Chile, Costa Rica, Mexico, and Peru). Adult patients (≥18 years) with retroperitoneal sarcoma who underwent surgery at six cancer centers in Latin America were included. Key outcomes were practice patterns, overall survival (OS), and progression-free survival (PFS). ResultsIn this retrospective study, 333 patients diagnosed with retroperitoneal sarcomas met the inclusion/exclusion criteria. The cohort consisted of 157 females (42.3 %) and 176 males (57.7 %), with an average age of 53.9 years (SD 13.37). Histology most commonly included Dedifferentiated Liposarcoma (31.5 %), Well-Differentiated Liposarcoma (29.7 %), and Leiomyosarcoma (9.9 %). The tumors predominantly resided in the retroperitoneum (81.7 %) and showed a mean diameter of 23.53 cm (SD 13.8 cm). Surgical interventions varied, with Complete Compartmental Resection performed in 31.2 % of cases and Simple Complete Resection in 29.4 %. Postoperative complications were documented, with Clavien-Dindo Grade ≥3 complications occurring in 16.8 % of patients. An R0/1 resection was obtained in 91.6 % of cases. The ICU admission rate post-surgery was 18.6 %. Adjuvant treatments included radiotherapy in 8.1 %. Local recurrence occurred in 20.7 % of cases, with the majority being ipsilateral. Distal recurrence was observed in 15 patients, predominantly affecting the liver. The mean overall survival was 65.5 months, and disease-free survival was 47.0 months. ConclusionThis study provides information on the epidemiology, treatment patterns, and outcomes of retroperitoneal sarcomas in a group of reference centers in Latin America. These results represent Latin America's largest body of evidence on retroperitoneal sarcomas.