bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological features and treatment profile of patients referred to a sarcoma medical oncology centre in India: Challenges and insights from the developing world.
Authors: Tansir Ghazal , Rastogi Sameer , Barwad Adarsh
Published: June 2023

e23533

Background: Sarcomas are rare cancers that warrant expert pathologic diagnosis (dx) and multidisciplinary treatment (MDT). We analysed details of patients (pts) diagnosed with soft tissue sarcomas (STS) and bone sarcomas (BS) referred to our centre. Methods: This is a retrospective study of pts diagnosed with STS or BS referred to All India Institute of Medical Sciences, Delhi between January 2021 and December 2022. Histopathological discrepancies were noted as change of primary dx or differences in grading or sarcoma subtyping on pathology review. Surgical and/or medical deviations from standard practise were identified. SPSS 26.0 was used for statistical analysis. Results: 268 pts with median age of 35 years (range 8 months-85 years) and male predominance (n = 140, 52.2%) were included. 121 (45%) pts belonged to adolescent and young age (AYA) group. 163 (61%) pts came from urban/semi-urban background and from a median distance of 90 miles (range 6.2-1587). Median symptom duration prior to referral was 9 months (range 6 months-12 years). Based on biopsy or cytopathological evidence, referred pts included 186 (69.4%) with STS, 73 (27.2%) with BS, 7 with undifferentiated sarcoma (2.6%) and 2 with carcinoma (0.7%). The most common STS (n = 186) were leiomyosarcoma (14%), synovial sarcoma (12%) and liposarcoma (8.3%); BS (n = 73) included osteosarcoma (44%), Ewing sarcoma (44%), chondrosarcoma (9.5%). Molecular and/or germline mutation tests were performed only in 9 of 131 (6.8%) indicated cases before referral. Localized/locally advanced and metastatic stages were found in 94 (35.6%) and 116 (43.2%) resp; rest (21.2%) did not undergo staging work-up outside. Common primary sites were extremity (n = 127, 44.4%), abdomen (n = 71, 24.8%), thorax (n = 24, 8.3%). 125 (43.7%) and 91 (31.8%) pts had undergone surgery and chemotherapy resp outside. 1st line chemotherapy (n = 85) was anthracycline-based (n = 65, 76.4%), ifosfamide-based (n = 6, 7%), gemcitabine-docetaxel (n = 5, 5.8%). 2nd line (n = 29) was gemcitabine +/- docetaxel (n = 7, 24.1%), anthracycline (n = 6, 20.6%), ifosfamide-based (n = 6, 20.6%), pazopanib (n = 6, 20.6%). Pathologic discrepancies found in 87 (30.4%) pts included change of primary diagnosis in 44 (15%), sarcoma subtype variation in 35 (12.2%) and benign disorder misclassified as malignancy in 5 (1.7%) pts. Deviations in chemotherapy (n = 43, 47.2%) included inadequate dose/cycles in 18 (42%), no chemotherapy despite indication in 8 (18.6%), non-standard regimens in 10 (23%) pts. Distance/rural residence did not correlate with pathology/treatment deviations. Conclusions: In this era of precision medicine and targeted oncology, our findings reflect the need for well-equipped diagnostic and treatment facilities. The lack of expert centres catering to pts with sarcomas remains a challenge in developing countries.
Genitourinary embryonal rhabdomyosarcoma clinicopathologic determinants of clinical outcomes: Analysis of a pooled database.
Authors: Graham Christopher , Yelamanchili Ankita , Amankwah Millicent , Haddad Philip A.
Published: June 2023

e23536

Background: Embryonal rhabdomyosarcoma (ERS) refers to malignant soft tissue tumors with phenotypical, histological features of primitive skeletal muscle. ERS commonly involves the head and neck region and genitourinary system. Genitourinary embryonal rhabdomyosarcoma (GUERS) is considered an entity similar to other ERS based on Intergroup Rhabdomyosarcoma Study Group (IRSG) with non-prostate GUERS considered low risk. This study seeks to define other high-risk subtypes in this population. Methods: To study the demographic and molecular characteristics, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 137 cases of GUERS. Kaplan-Meier survival curves, Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results: 137 patients with confirmed GUERS were identified: median age was 16 and F:M ratio of 1.6. Female reproductive organs (49%), renal and urinary tract (24%), male reproductive organs (23%), and abdomino-pelvis (4%) were involved. Lymph node involvement and metastasis occurred in 11% and 13%, respectively. Staging consisted of stage I (65%), stage II (15%), stage III (8%), and stage IV (12%). Rhabdomyosarcoma clinical groups were mostly IA (41%), IIIA (31%) and IV (13%). Risk groups consisted of low (71%), intermediate (17%), and high (13%). Median OS and DFS were 96 and 42 months, respectively. The primary site of involvement impacted OS, with urinary tract organ involvement having the best median OS, compared to female reproductive organs, male reproductive organs, and abdomino-pelvis involvement (p = 0.01). While primary pelvic disease (p = 0.03), prostate (p = 0.008), and lymph node involvement (p = 0.001) were associated with worse OS, cervix/vaginal involvement tended to have better OS (p = 0.06). Constitutional symptoms (p = 0.0007), obstruction (p = 0.047) and metastases (p = 0.02) were associated with worse OS. Clinical staging system (p = 0.0008), risk groupings (p = 0.06) correlated with OS, but not clinical groupings (p = 0.26). GUERS with vimentin+, CD99- and SMA+ had worse survival (only the latter was statistically significant). Compared to no treatment, RT, CT+/-RT, S+CT+RT were superior with mOS of 2, 6, NR, 96 months, respectively (p < 0.0001). Achieving CR had superior OS (p < 0.0001). OS was not impacted by age, sex, or extent of surgery. Conclusions: Genitourinary embryonal rhabdomyosarcoma is a distinct clinical entity with outcomes worse than other forms of ERS defined by the Clinical Groups of IRSG. Prostate, primary pelvic and obstructive symptoms have worse OS compared to bladder and cervical involvement and we propose their inclusion in the current Clinical Group. This study presents updated clinicopathologic data from a pooled cohort of patients with GUERS.
Head and neck embryonal rhabdomyosarcoma clinical outcomes determinates: A pooled database analysis.
Authors: lakra rachaita , Haddad Philip A. , Zaheer Usman , Graham Christopher
Published: June 2023

e23537

Background: Embryonal rhabdomyosarcoma (ERS) is a soft tissue sarcoma of skeletal muscle with mesenchymal precursor cells that involve the genitourinary system or head and neck. Currently, head and neck embryonal rhabdomyosarcoma (HNERS) is considered a similar entity to other ERS subtypes by the Intergroup Rhabdomyosarcoma Study Group (IRSG), with only parameningeal disease being considered as high risk. We seek to identify other higher risk phenotypes in this population. Methods: To study the demographic, molecular and IHC characteristics, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 101 cases of HNERS. Kaplan-Meier survival curves, Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: 101 patients with confirmed HNERS were identified: median age of 6.5 years, male predominance with M:F ratio of 1.7. While R0 was achieved in 44%, surgical R1 and R2 were feasible in 13% and 44% of the cases. HNERS involved the following anatomic sites: Parameningeal (49%), Skull (40%), Maxilla (39%), Nasopharynx (34%), Ears (25%), Oropharynx (17%), Nervous system (16%), Larynx (14%), Mandible (12%), Internal Jugular (7%), Orbit and Carotids (6% each), Tongue (3%), and thyroid (2%). Lymph nodes, and bone marrow were involved in 11% and 2%, respectively. Metastases occurred in 4%. The stage distribution consisted of stage I (41%), stage II (34%), stage III (19%), and stage IV (6%). Clinical groups comprised: IA(23%), IB(4%), IIA(8%), IIB(3%), IIIA(45%), IIIB(12%), and IVA(4%). Risk groups consisted of low (53%), intermediate (41%), and high (6%). The cohort’s median DFS was 240 months whereas the median OS was not reached. OS was negatively affected by parameningeal (p = 0.01), nasopharyngeal (p = 0.02), ear (p = 0.02), nerve (p = 0.0001), bone (p = 0.002), and LN (p = 0.0004) involvement. The presence of metastases was associated with worse OS (p = 0.0001). The IRSG staging system (p < 0.0001), the risk groupings (p = 0.0001), and the clinical groupings (p = 0.06) correlated with OS, though the latter did not reach statistical significance. Compared to no treatment, localized therapies such as surgery and radiation therapy, and combination chemotherapy had statistically significant improvement in OS (p = 0.027). Achieving CR was associated with superior OS (p < 0.0001). OS wasn't impacted by age, sex, extent of surgery, IHC, BM involvement or other head and neck anatomic site involvement. Conclusions: Embryonal Rhabdomyosarcoma of the Head and Neck is a distinct clinical subtype of ERS not fully defined by IRSG clinical groups when compared to other types of embryonal rhabdomyosarcoma. Parameningeal, nasopharyngeal, ear involvement had poor OS and should be considered as a clinical grouping. This study presents updated data from a pooled cohort of patients with HNERS.
Phase I study of anlotinib in pediatric patients with high-risk, recurrent, or refractory sarcomas.
Authors: Lu Suying , Wang Juan , Sun Feifei , Huang Junting , Zhu Jia , Cai Ruiqing , Zhen Zijun , Zhang Yizhuo
Published: June 2023

e23538

Background: Anlotinib is an orally available, highly potent, novel multitargeted tyrosine kinase inhibitor, which blocks VEGF signaling by selectively targeting VEGFR-2, -3 as well as FGFR-1, -2, -3, -4 with high affinity. We evaluated the toxicity, and pharmacokinetic profile of anlotinib in children with high-risk, recurrent, or refractory sarcomas. Methods: This was an open-label, single-center, single-arm phase I study, which enrolled pediatric patients with sarcoma. Pediatric patients aged 5-18 years diagnosed with high-risk, recurrent, or refractory sarcomas were enrolled and further categorized into cohort A (＜35 kg) or cohort B (≥ 35kg). Anlotinib was administered orally, once daily, 2-week on off, until disease progression, death, unacceptable toxicity, or withdrawal of consent for any reasons. A fixed anlotinib level of 8 mg was given to cohort A and three dose levels (8mg, 10mg, 12mg) were evaluated using a “3 + 3” design in cohort B. Results: Between December 29, 2020, and September 7, 2022, 34 patients were enrolled to evaluate the safety and 19 (55.9%) were evaluable for efficacy. The median age was 12 (range 5-18) years old. The main subtype eligible was rhabdomyosarcoma (23.5%). Two of fifteen patients in cohort A at a dose level of 8 mg experienced dose-limiting toxicity, including grade 3 hematuria and grade 3 hand-foot syndrome. The grade 3 treatment-related adverse events (AEs) included neutropenia (3 [8.8%]), hand-foot syndrome (2 [5.9%]), headache (1 [2.9%]), hematuria (1 [2.9%]), hypertension (1 [2.9%]), and hyperbilirubinemia (1 [2.9%]). The most common AEs were grade 1 or 2 hypothyroidism (58.8%) and abdominal pain (55.9%). Twelve of 19 (63.2%) patients had a best response of stable disease with seven patients receiving ≥ 6 cycles. Age has no significant effect on the level of body exposure per unit body surface area dose, and patients younger than 12 years old had a faster elimination. Conclusions: Anlotinib in pediatric patients with sarcoma was well tolerated. The RP2D of anlotinib for future studies is 8 mg for patients＜ 35 kg and 12 mg for patients with ≥ 35kg. Clinical trial information: NCT04659733 . [Table: see text]
Study of microwave ablation in patients with unresectable soft tissue sarcoma.
Authors: Weitao Yao , Du Xinhui
Published: June 2023

e23545

Background: Currently, the main treatment for soft tissue sarcoma is a combination of radiotherapy, chemotherapy and complete surgical resection. However, there is no ideal method for soft tissue sarcoma after multiple recurrences, large tumours, insensitivity to radiotherapy or failure of down grade therapy. Microwave ablation is one of the main techniques for tumour thermal therapy, but its use in soft tissue sarcoma is not yet widespread. The aim of this study was to investigate the safety and efficacy of microwave ablation in refractory soft tissue sarcoma. Methods: Fourteen eligible patients with refractory soft tissue sarcoma were treated with local anaesthesia, multi-point intra-tumour needle placement under ultrasound guidance and local radiofrequency ablation (20-40 J, 2-5 minutes). For tumours larger than 5 cm in diameter, repeat ablation can be performed after 3-4 weeks. Of the 14 patients, 8 were male and 6 were female, with a mean age of 58.91 years. There were 4 cases of myxofibrosarcoma, 3 cases of dedifferentiated liposarcoma, 2 cases of malignant nerve sheath tumour, 2 cases of clear cell sarcoma and 3 cases of other sarcomas. Tumours were located in the trunk in 7 cases, in the upper limbs in 3 cases and in the lower limbs in 4 cases. Of these, 5 patients had two operations and 9 patients had three or more operations. Four cases had received first-line therapy, five cases had received second-line therapy, and five cases had received third-line therapy or more. Postoperative pain relief and wound complications were recorded. MRI was performed regularly to assess tumour shrinkage. Results: Post-operatively, all patients experienced a significant reduction in local swelling and pain. Post-operative imaging showed partial response (PR) in 11 cases and stable disease (SD) in 3 cases. The overall response rate (ORR) was 78.57%. Progression-free survival (PFS) ranged from 2-18 months with a median of 5.82 months. Complications included tumour ulceration in 2 cases, skin burns with necrosis in 2 cases and postoperative fever in 5 cases. Conclusions: For soft tissue sarcomas that cannot be removed by surgery, where tumour growth is slow and insensitive to radio/chemotherapy, local microwave ablation can achieve tumour shrinkage and reduce patient symptoms such as local swelling and pain. It is an effective treatment option for some specific sarcoma patients.
A phase II study of fruquintinib in the first- (1L) or second-line (2L) treatment of unresectable metastatic soft tissue sarcoma.
Authors: Luo Zhiguo , Zhang Xiaowei , Zhao Ting , Zheng Bi-Qiang , Yan Wangjun , Chen Yong , Xu Yu , Wang Chun-Meng , Zhang Junhua , Wang Jian , Yu Lin , Liu Xin
Published: June 2023

e23547

Background: Standard treatment for patients with unresectable metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if fruquintinib, a highly selective tyrosine kinase inhibitor of VEGFR-1, -2, and -3 is effective and safe in the 1L or 2L treatment for these patients. Methods: This is a single-arm, prospective, single-center clinical study. The inclusion criteria were patients with pathologically confirmed unresectable metastatic STS (including desmoplastic small round cell tumors, epithelioid hemangioendothelioma, hemangiopericytoma/malignant solitary fibroma, and chemotherapy-failed hemangiosarcoma), at least one measurable lesion (according to RECIST 1.1), with the normal function of main organs. Other inclusion criteria included ECOG PS 0-2 and anti-angiogenesis treatment naïve. Patients were administrated 5mg fruquintinib once daily for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. The primary study endpoint was Progression free survival (PFS). Objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and adverse event was also calculated. Results: Data cutoff date was January 31 2023. 14 patients (9 males and 5 females) were enrolled. The median age is 50.1 (range 21-69). Pathological types included: Hemangiopericytoma/malignant solitary fibroma (n=6); Epithelioid Hemangioendothelioma (n=6) and Hemangiosarcoma (n=2). 2 patients were died, the median PFS was 8.1 m. 14 patients were eligible for the evaluation of tumor response. 3 patients (2 cases of Hemangiosarcoma and 1 case of Epithelioid Hemangioendothelioma) achieved partial response (PR) and the ORR was 21.4 %(3/14). 10 patients had stable disease (SD) and the DCR was 92.9% (13/14). Most adverse events were hypertension, fatigue, and hemorrhage. The most Grade 3/4 adverse effect is hypertension and abnormal liver function. Conclusions: The fruquintinib showed a promising efficacy and favorable tolerance in the 1L or 2L treatment of unresectable metastatic soft-tissue sarcoma. Clinical trial information: NCT05142631 .
Comparative analysis between the 8th and 7th AJCC as a prognostic tool for patients diagnosed with nonmetastatic head and neck soft-tissue sarcoma.
Authors: Brito Angelo Borsarelli Carvalho , Zanetta Giulia Kodja , Costa Felipe D'Almeida , Formiga Maria Nirvana da Cruz , Mello Celso Lopes , Filho Joao Goncalves , Ikeda Mauro Kazuo , Camillo Cláudia Malheiros , Pinto Clovis Antonio Lopes , de Jesus Victor Hugo Fonseca , Campos Fernando Augusto Batista , Kowalski Luiz Paulo , Nicolau Ulisses Ribaldo
Published: June 2023

e23550

Background: Head and neck soft-tissue sarcoma (HN-STS) is a rare entity for which a new prognostic risk stratification has been proposed in the 8th AJCC. The tumor size 2cm and 4cm have been adopted as cutoffs for T1 to T3 classification and the invasion of surrounding structures denotes T4. In opposite, in the 7th edition the primary tumor size of 5 cm determines T1 and T2 classification. This study aimed to compare the 8th and 7th AJCC as a prognostic tool for HN-STS. Additionally, we sought to investigate prognostic factors in this group of patients. Methods: This is a single Tertiary Hospital study approved by the institutional ethical review committee from the AC Camargo Cancer Center. We retrospectively evaluated patients with non-metastatic HN-STS whose histology subtypes are included in the 40th chapter of the 8th AJCC version. We compared the AJCC 7th and 8th T staging with Cohen’s kappa coefficient using inter-rater agreement analysis. The Kaplan-Meier (KM) estimator was used to calculate median survival times; differences in time-to-event outcomes were assessed using the log-rank test. Cox proportional hazard model was used to assess the effect of features in overall survival (OS). Results: Ninety-five HN-STS treated with curative intent from 2005 from 2021 patients diagnosed were evaluated. Surgical resection (94.7%), radiotherapy (48.4%) and chemotherapy (23.1%) were the employed therapeutic approaches. Leiomyosarcoma and liposarcoma (10 of each subtype) were the most common histology subtypes; High grade disease was present in 66.3%. Kappa coefficient of inter-rater agreement was 0.46 with statistical significance (p = 0.03), which indicates poor agreement between AJCC 7th and 8th T staging system. Regarding OS stratified by T size in the AJCC 7th (T1 and T2) and 8th (T1, T2, T3 and T4) was not statistically different between groups (P = 0.83 and P = 0.21, respectively). Patients with T4 (47.6% vs 78.7%, P = 0.04) and high grade (64.0% vs 96.2%, P = 0.003) had worst 5-years OS. In Cox multivariate analysis, patients with 8th edition T4 and high grade had 3.15- and 4.16-fold increased risk of death, respectively. Conclusions: In our series of patients with HN-STS, neither 7th nor 8th AJCC T size category groups discriminated prognosis. Tumor with local invasion (8th AJCC T4) and high grade were all associated with increased risk of mortality.
Presentation of congenital soft-tissue sarcomas: A single institution experience.
Authors: Parra Del Riego Angela , Olsen Braden , Gonzalez Keishla , Pabon Camila , Chamyan Gabriel , Fader Maggie Eidson
Published: June 2023

e23551

Background: Pediatric sarcomas make up 10% of pediatric tumors and involve a varied range of histological patterns with different prognosis which creates therapeutic challenges. Neonatal presentation is rare among sarcomas and poses further challenges in therapy. Methods: We present 5 cases of congenital sarcomas reporting pathology, genetics, treatment, and outcomes. We retrospectively identified 5 patients with sarcomas diagnosed in the neonatal period from a single institution in Miami from 2017 – 2022 in order to identify similarities between neonatal sarcomas. Our sarcomas included an embryonal rhabdomyosarcoma (RMS), infantile fibrosarcoma (IFS), rhabdoid tumor, and two undifferentiated sarcomas. Results: The presentation occurred between birth and four days old. Location at presentation was varied. Four of our patients were Nonrhabdomyosarcoma Soft Tissue Sarcomas (NRSTS). Only one patient was diagnosed prenatally, while three were diagnosed at birth, and one at 4 days of life. Three patients presented spindle cell pathology. One of our undifferentiated sarcomas was classified as IFS-like, Archer FusionPlex was negative for mutation. Our other undifferentiated sarcoma showed a COL1A1 gene rearrangement on chromosome 17q.21 with immunostains positive for BCOR, SMARCB1, SMARCA4. Congenital fibrosarcoma showed ETV6 fusion with NTRK and immunostains positive for FLI-1, SMA, CD34, INI-1. The RMS showed focal loss of PTCH1 and FANCC and had immunostains positive for desmin and myogenin. The metastatic rhabdoid tumor showed SMARCB1 whole gene deletion as well as a 570kB deletion in chromosome 22q11.23. Three patients were treated on ARST 0331 with vincristine, doxorubicin, and cyclophosphamide (VAC), with the undifferentiated sarcoma requiring advancement to ARST 0332. The patient with metastatic rhabdoid tumor was treated with AREN 0321. Four patients required surgery. We had 1-year-survival in three patients, all treated on ARST 0331 or ARST 0332. The patient with metastatic rhabdoid tumor died at 4 months of age while on AREN 0321, and our patient with IFS-like sarcoma decompensate and died at ten days old, prior to starting therapy. Conclusions: We show multiple genetic mutations with SMARCB1 alteration in both an undifferentiated sarcoma and a malignant rhabdoid tumor but otherwise found no significant pattern among individual sarcomas. Our cases show good outcomes for patients qualifying for ARST 0331. We highlight the need for improved methods of detection of pediatric tumors in utero.
Concordance between orthotopic-patient derived xenograft models and patient treatment responses.
Authors: Nakashima Jonathan , Sperry Jantzen , Lofftus Serena , Federman Noah , Singh Arun S. , Eilber Frederick C.
Published: June 2023

e23553

Background: Patient-derived xenografts (PDX) have shown promise in identifying personalized therapies for cancer patients. We have previously shown that orthotopic-PDX models from untreated, high-grade sarcomas demonstrate a 62% establishment rate with a median time of 54 days. Methods: We performed a retrospective study by collecting oncologic patient treatment history and response data to carry out in vivo pharmacology studies on corresponding O-PDX models using therapies that the patients received. Results: Among 16 patients and 26 therapies, we identified an overall concordance of 84.6%. Specifically, we show a positive predictive value of 82.4% among responders and a negative predictive value of 88.9% among non-responders. Conclusions: This study demonstrates that O-PDX models replicate clinical response in patients and are valuable screening platforms for guiding therapeutic decision-making for rare cancers such as sarcoma.
Analysis of demographic characteristics of malignant peripheral nerve sheath tumor in adults: A National Cancer Database study.
Authors: Voth Caitlyn , Wu Xinxin , Keirns Darby , Silberstein Peter T. , Hsia Beau
Published: June 2023

e23555

Background: Malignant peripheral nerve sheath tumor (MPNST) is a rare cancer involving the peripheral nerve sheath. Even though the 5-year post-surgical resection survival rate is only 30 to 40%, the epidemiology is not well understood, and looking at trends in demographics could provide insight into factors potentially contributing to poor prognosis. A previous National Cancer Database (NCDB) study investigated demographics in pediatric patients with MPNST. This study analyzed NCDB data to investigate the demographics of adults with MPNST. Methods: Adult patients with a histologic diagnosis of MPNST were retrospectively examined in a cohort analysis using demographic information from the NCDB from 2004 – 2020 (N = 414). Regression analysis was used to describe incidence trends. Demographics (age, sex, race, Hispanic origin, income, insurance status, area of residence, facility type, distance from facility, and Charlson-Deyo score) were explored through descriptive statistics. Palliative care enrollment and mortality rate was examined. Results: 414 patients with age > 18 were identified in the NCDB database with a confirmed diagnosis of MPNST between the years 2004 – 2020. There was a slight increase in incidence of patients diagnosed per year (R2 = 0.254). The average age of diagnosis was 47.0 years (SD = 17.2, range = 19 – 88 years) with more males (51.4%) affected than females (48.6%). The most common primary sites were the retroperitoneum (32.4%), spinal cord (24.4%), and cranial nerves (15.0%). A majority of individuals (82.6%) had Charlson-Deyo comorbidity scores of 0. Individuals most commonly affected were White (79.7%) or Black (14.3%), and non-Hispanic (87.4%). Patients most commonly were in the top quartile of household income (31.6%), had private insurance (53.6%), lived in metropolitan counties (83.8%), and received treatment at an academic/research program (62.2%). Patients lived on average 61.6 miles (SD = 145.7, range = 0.5 – 1454.9) from the facility. The 90-day mortality rate post-surgery was 10.5%. The overwhelming majority of patients did not receive palliative care (94.4%). Conclusions: This is the first NCDB analysis on the demographics of MPNST in adults, providing information that bridges the gap in knowledge. This analysis showed that the retroperitoneum was the most common tumor site, and that the average age of diagnosis was 47 years, consistent with previous reports. Patients were most likely to be White, non-Hispanic, upper quartile income earners, privately insured, treated at an academic facility, and live in metropolitan counties. With the majority of patients receiving no palliative care, it’s possible that palliative care is underutilized and may benefit MPNST patients given the poor prognosis. Additional research on the relationship between socioeconomic status and palliative care access may provide information on this discrepancy.
Do future innovations in development influence oncologists’ treatment recommendations today? A survey of U.S. oncologists.
Authors: Li Meng , Elsisi Zizi , Wong William Bruce , Kowal Stacey , Veenstra David L , Garrison Louis P.
Published: June 2023

e24004

Background: Survival benefit from current anticancer treatments, even if modest, improves a patient’s chances of accessing and benefiting from future innovations currently in clinical development. No studies to date have evaluated the potential impact of future innovations on oncologists’ treatment recommendations. Methods: We conducted a national survey of medical and hematologic oncologists (n = 200) on how expectations about future innovations may influence their treatment recommendations today. The survey described a hypothetical patient with metastatic cancer, whose median overall survival (OS) was approximately 6 months with most dying within 2 years. We presented four alternative hypothetical scenarios of new innovations in the clinical development pipeline with varying (a) expected efficacy—“modest” (improvement in median OS of 2 months} or “breakthrough” (improvement in median OS of 6 months) and (b) time of arrival (in 6 months or 1 year). We asked the oncologists about the likelihood (using a 5-point Likert scale) (1) that they would discuss these new innovations with the hypothetical metastatic patient, and (2) that these new innovations would influence their recommended treatment for the patient today. We descriptively summarized percentages of oncologists who responded “likely” or “very likely” and examined their associations (using multivariate logistic regression) with the expected efficacy and time of arrival of future innovations as well as the characteristics of oncologists and their practice. Results: When future innovations were expected to have modest efficacy and arrive in 6 months, 61% of oncologists reported that they would be likely or very likely discuss them with their patients, and 52% reported new innovations would influence their treatment recommendations today. With modest efficacy and time of arrival in 1 year, percentages dropped to 49% and 41%, respectively. With breakthrough efficacy and arrival in 6 months, 76% would discuss and 68% would consider new innovations. With breakthrough efficacy and arrival in 1 year, percentages dropped to 62% and 55%, respectively. Greater expected efficacy and shorter time to arrival were associated with a significantly greater likelihood of discussing a future innovations with patients across oncologist and practice characteristics (adjusted odds ratios: breakthrough vs. modest = 1.75; 6 month vs. 1 year = 1.72). Conclusions: Future treatment innovations in clinical development are relevant for decision-making today even when anticipated time to arrival is two times the current median OS. results indicate that it is important to include future innovations in shared decision-making in addition to the benefit-risk balance of current treatments.
One way to provide effective healthcare services for patients with advanced cancer to improve their quality of life and survival: Prediction modeling using machine learning techniques and causal relationship between self-management strategy, health-related quality of life, and survival.
Authors: Jung Juyoun , Jung Kyung Hae , Koh Su-Jin , Yun Young Ho
Published: June 2023

e24005

Background: In healthcare services, self-management strategies can play a crucial role in enhancing the health-related quality of life (HRQoL) or survival of cancer patients, regardless of their stage or treatment plan. However, there needs to be more research addressing the relationship between the strategies, HRQoL, and survival. To address this gap, we investigated the relationship between the strategies, HRQoL, and survival using machine learning techniques (MLT) and path analysis with structural equation modeling (SEM). Methods: This study was a secondary analysis of a randomized controlled trial (RCT) to provide early palliative care to individuals with advanced cancer (ClinicalTrials.gov, ID NCT03181854). We employed dimensional multiple Cox proportional hazard regression analyses to identify the crucial predictors of 1-year survival. By integrating the critical predictors extracted from the Cox regression models, we established a final survival prediction model using the eXtreme Gradient Boost (XGBoost) and the BorutaSHAP in MLT. Furthermore, we used path analysis to investigate the causal relationship between the strategies, HRQoL, and survival. Results: The univariate dimensional Cox models indicated that factors such as worse ECOG performance status (hazard ratio (HR) = 2.18), living alone (HR = 1.74), male (HR = 1.65), low global QoL (HR = 1.81), high dyspnea (HR = 2.30), high pain (HR = 1.75), high appetite loss (HR = 1.94), high constipation (HR = 2.11), high depression (HR = 2.79) at baseline, and no significant positive changes in emotional functioning (HR = 1.88) negatively impacted survival. The final XGBoost model for survival prediction using repeated K-fold methods (K = 5, repeats = 20, area under the receiver operating characteristic curve (AUROC) = 0.76, area under the precision-recall curve (AUPRC) = 0.87) and bootstrapping (n = 300, AUROC = 0.81, AUPRC = 0.91) showed high survival prediction performance. Additionally, the path analysis revealed a causal relationship between self-management strategies, HRQoL, and survival in patients with advanced cancer ( p-value = 0.005). HRQoL was found to have a complete mediating relationship between the strategies and survival. Self-management strategies did not directly correlate with survival but showed an impact on survival through HRQoL. Conclusions: To the best of our knowledge, this is the first study to uncover the connection between self-management strategies, HRQoL, and survival in patients with advanced cancer using MLT and path analysis. These findings have the potential to deepen our understanding of self-management strategies and aid healthcare providers in providing improved cancer care for patients with advanced cancer. Clinical trial information: NCT03181854 .
The financial toxicity of chemotherapy in Belize.
Authors: Wong Wayne , Dickerson James , Lattin John , Ohanian Alec , Habet Marta , Bernard Margaret , Huang Franklin W. , Yacab Ramoncito Argenes
Published: June 2023

e24007

Background: In low- and middle-income countries (LMICs) such as Belize, large fractions of healthcare costs are borne directly by patients. In these settings of minimal insurance coverage and a fragmented healthcare system, evaluating the extent of financial toxicity is paramount to understanding direct barriers to care delivery. We surveyed Belizean cancer patients in 2022 who were receiving chemotherapy at the only public oncology clinic in the country, established at the Karl Heusner Memorial Hospital (KHMH) in 2018, to quantify financial toxicity. Methods: A convenience sample of patients at the KHMH oncology clinic were surveyed between February and March 2022. Patients who consented during their infusion appointment were given a tablet with a 21-question survey (English or Spanish). This survey was developed from the FACT-G and COST tools adapted specifically for LMIC settings. Answers were on a 5-point Likert scale. We provide descriptive statistics of the population and survey responses. Results: Median age of survey participants (n = 32) was 51 (IQR 43 – 62), 84% were female and 53% unemployed. 71% were uninsured. Those insured were covered by the Belizean government’s National Health Insurance which does not include oncologic care. Most patients (72%) had traveled from another district for treatment at the clinic in Belize City. Cancer types represented were breast (42%), gastrointestinal (27%), gynecologic (27%), and lymphoma (4%); 75% of patients had either stage 3 or 4 disease. 56% agreed with the statement “I am having financial problems with cancer treatment,” 31% disagreed, and 13% neither agreed nor disagreed. Patients were allowed to indicate multiple contributors to financial hardship during treatment, with costs of chemotherapy cited most often (50% of patients), followed by transportation costs (38%), hospital fees (22%), food (12%), and housing (9%). 25% of respondents agreed with the prompt “It is difficult to come to all of my appointments,” with transportation being the most cited reason (88%). Conclusions: In our survey, more than half of Belizean cancer patients on chemotherapy reported financial hardship with their treatment. Drivers of toxicity were the cost of chemotherapy and travel. Our sample, predominately female, unemployed, uninsured, and from less wealthy districts, had sociodemographic factors that suggest a high risk for financial toxicity during cancer treatment. Though limited by the small sample size, this study prompts further investigation and more precise quantification of financial toxicity in Belize. These preliminary data have begun conversations within the Ministry of Health for inclusion of chemotherapy under the covered medications list by public health institutions.
Clinical benefit (rate) of geriatric assessment in a Veterans Affairs (VA)-based oncology clinic according to the Geriatric 5Ms framework.
Authors: Gregorio Dave , Shaker Sarah , Powers Becky , Arora Sukeshi Patel , Banwait Ranjit Singh , Datta Paromita
Published: June 2023

e24010

Background: The geriatric assessment (GA) is a validated, multi-system assessment tool that can detect vulnerabilities often not captured with standard oncology assessments in older adult patients with cancer. The Geriatric 5Ms is a novel communication framework used to describe core competencies in geriatrics. Prior studies have shown GA integration in oncology practice can significantly reduce grade 3 or higher chemotherapy-related toxicities, falls, polypharmacy, hospital length of stay (LOS), increase completion of advanced directives, and improve quality of life measures. Despite these benefits, implementation into clinical practice has remained low. This study aimed to utilize telemedicine to integrate GA into a busy VA oncology practice. Methods: In this quality improvement study design, we enrolled adult patients aged 70 years and older with solid tumors or hematologic malignancy, either newly established or receiving active systemic treatment through an urban, academic VA oncology clinic. Patients were assigned to the intervention (GA conducted via telemedicine by a geriatric specialist) if they scored ≤14 on G8, a validated screening tool. Outcomes were compared with a historical control cohort who received usual care (no virtual GA). Reported here are the clinical benefits measured qualitatively according to the geriatric 5Ms framework. Results: Between January 1, 2022 and March 30, 2022, we enrolled 116 patients (n = 57 intervention, 59 control) from a US VA-based population. Patients had a mean age of 76.8 (SD 6.2) between both cohorts and all patients were male (100%). Among patients in the intervention cohort, all patients (100%) derived benefit in at least one element of the 5M’s framework (Mind, Mobility, Medications, Multicomplexity, and Matters Most) from GA. Based on findings from the GA, services were provided in each of the 5M’s categories in the following frequencies: multicomplexity (88%), matters most (71%), medication (58%), mentation (50%), and mobility (46%). Conclusions: Incorporating GA via telemedicine into routine oncologic care was feasible within this VA-based population of older adult patients with cancer. Further, this project led to clinic recognition as an Age Friendly Health System by the Institute for Healthcare Improvement (IHI). When routinely performed, geriatric assessment led to clinical benefit among all patients receiving the intervention according to the 5M’s framework. Future studies will compare the clinical benefits of this intervention to clinical outcomes measures such as hospital length of stay, emergency room utilization, therapy toxicity, and survival among this patient population.
The role of Chinese acupuncture plus herbal decoction for chemotherapy induced cognitive impairment in elderly cancer patients.
Authors: Lv Guangmei , Hu Meng , Liang Wei , Wan Haijun Wan , Zhao Sunyan , Ha Wentao , Gong Yongling
Published: June 2023

e24018

Background: Elderly cancer patients would suffer cognitive impairment due to chemotherapy, and a series of neurocognitive symptoms, known as "chemobrain". Chinese acupuncture plus herbal decoction is an emerging therapeutic option for chemotherapy-induced cognitive impairment in elderly cancer patients, despite limited supporting evidence. By evaluating this novel Chinese medicine mode in elderly cancer patients at our institution, we aimed to contribute to the existing knowledge in this area while establishing a basis for further research. Methods: We performed a retrospective review of all cases of “chemobrain” related elderly cancer patients treated with Chinese acupuncture plus herbal decoction between 2019 and 2022. We identified 168 elderly cancer patients with clinically confirmed chemobrain; 83 were treated with electroacupuncture (2 sessions per week over 8 weeks) plus herbal decoction(Chines herbal medicine); 85 received either conventional drug therapy, or palliative-intent therapy. The Montreal Cognitive Assessment(MoCA) served as the primary outcome. Digit span test was the secondary outcome for attentional function and working memory. The quality of life and multiple functional assessments were also evaluated. Results: Those with Chinese acupuncture plus herbal decoction had much better performance than the remainder(as control), reverse digit span test at Week2 and Week8, with medium eﬀect size of 0.53 and 0.48, respectively, the difference in MoCA score and prevalence of chemobrain between cohorts was underpowered and not statistically significant. Higher baseline ECOG and comorbidity was noted in the latter cohort. Conclusions: These results suggest that Chinese electroacupuncture plus herbal decoction might have particular beneﬁts in reducing chemotherapy-induced working memory impairment and could markedly reduce various side effects caused by cytotoxic chemotherapy drugs.
Thyroid dysfunction and immune checkpoint inhibitors: Effect on survival in elderly patients.
Authors: Donisi Clelia , Pretta Andrea , Lai Eleonora , Liscia Nicole , Cadoni Andrea , Persano Mara , Mariani Stefano , Pinna Giovanna , Spanu Dario , Saba Giorgio , Migliari Marco , Dubois Marco , Atzori Francesco , Dessì Mariele , Puzzoni Marco , Pusceddu Valeria , Ziranu Pina , Madeddu Clelia , Massa Elena , Scartozzi Mario
Published: June 2023

e24020

Background: Aging inevitably leads to an accumulation of senescent cells, and immune system cells aren't an exception. They can contribute to a pro-inflammatory state and be involved in the immune escape of cancer cells through a boosted PD-L1 expression. Immunocheckpoint inhibitors (ICIs) represent the standard of care in several cancer histotypes, and immune-related adverse events (irAEs) seem to be associated with better outcomes. ICIs represent a valid therapeutic agent in elderly patients too. However, there is a lack of data on irAEs and outcomes correlation in this subgroup of patients. This retrospective-prospective study aims to evaluate the relationship between thyroid dysfunction and progression-free survival (PFS) and overall survival (OS) in elderly patients undergoing ICIs. Methods: From January 2019 to January 2023, we retrospectively collected data from 65 elderly patients under treatment with ICIs at the Medical Oncology Unit of the University Hospital and University of Cagliari, Italy. All patients were affected by stage IV disease. The primary endpoint was PFS and the secondary endpoint was overall survival OS. Statistical analyses were performed using the MedCalc Statistical Software Version 20.216. Results: The median age was 76 (± 5,5); 15.38% were female, whereas 84.62% were male. The histologies were: melanoma (26.9%), lung cancer (48.0%), kidney cancer (15.3%), and colorectal cancer (9.8%). Compared to those without thyroid dysfunction during immunotherapy treatment, individuals with thyroid irAE had, at univariate analysis, longer median PFS (68 versus 26 months, p = 0.02, CI 95% 18.0-68.0, HR 0.29 0.10-0.83) and longer median OS (59 versus 39 months, p = 0.04, CI 95% 25.0-90.0 HR 0.50 0.25-0.99). Conclusions: In an era where biomarkers for immunotherapeutic agents are lacking, thyroid dysfunction irAE could be a predictive factor of better PFS and OS in elderly patients affected by cancer of various histology.
Validation of the distress thermometer score in a geriatric oncology population.
Authors: Zuber Charlotte , Swartz Kristine , Chapman Andrew E. , Rhodes Lora , Zhan Ting Ting , Wen Kuang-Yi
Published: June 2023

e24030

Background: The geriatric oncology population is uniquely vulnerable to increased levels of psychological distress due to age related challenges such as social isolation, change in lifestyle, and comorbid conditions. In the general population, higher levels of psychological distress have been shown to impact treatment course, quality of life, and survival. The NCCN Distress Thermometer (DT) is a validated fast and effective screening tool for psychological distress, with a cutoff score of 4 yielding optimal sensitivity and specificity in a general cancer population. However, the best cutoff for detecting psychological morbidity in older cancer patients is unclear. In this study, we aim to compare the sensitivity and specificity of various cutoff values for the Distress Thermometer score to predict Geriatric Depression Scale (GDS) score. Methods: Data is derived from 242 geriatric oncology patients from the Senior Adult Oncology Center at Jefferson Health. Using a cutoff of 5 for the GDS as the clinical standard guideline, we use receiver operating characteristic (ROC) curve analysis of the univariable logistic regression model to predict clinical depression. Results: A cutoff DT score of 3.5 was found to be most sensitive and specific (0.66,0.68) for predicting clinical depression (Area Under the ROC Curve (AUC) = 0.70). Multivariable logistic regression including age improved the predictive ability of the DT score to an AUC of 0.75. Conclusions: The increase in AUC with the addition of age indicates the potential use of a composite value of age and DT score to best determine at-risk patients in a clinical setting. While these results indicate the utility of the Distress Thermometer as an effective screening tool in the geriatric oncology population, our findings also suggest that a lower threshold score is advised for clinicians who are hoping to identify older cancer patients who are distressed. Patients who meet the threshold criteria would then be assessed further for triage into appropriate levels of geriatric supportive services.
Risk factors for falls and fear of falling among older patients with cancer.
Authors: Gomaa Sameh , Swartz Kristine , Chapman Andrew E. , Zhan Tingting , Wen Kuang-Yi
Published: June 2023

e24032

Background: Cancer is a disease of the elderly with more than 60% of all cancers diagnosed in adults age 60 or older. Falls pose a substantial risk for older cancer patients leading to hip fractures, traumatic brain injury, and are the leading cause of injury-related hospitalizations in persons aged 60 and older. This risk is due to aging changes compounded by the effect of cancer and cancer therapy. This report aims at understanding risk factors for falls and the perception of fear of falling (FOF) among older patients with cancer. Methods: As a single-site, retrospective cohort study, data was derived from 249 geriatric oncology patients from Senior Adult Oncology Center at Jefferson Health. The primary endpoints are the number of falls in the preceding 12 months and FOF as part of a self-reported fall screening. Multivariate logistic regression model was used to identify the independent risks factors by including patients’ age, sex, race/ethnicity, BMI, polypharmacy, cancer types, ECOG scores, Timed up and go (TUG) test, CARG toxicity scores, Mini-Cog, frailty status and depressive symptom for each endpoint separately. Results: Majorities were White (62.1%) and female (57.2%) with a mean ages of 78.1 (SD = 8.7). The most common cancers diagnosed were hematologic malignancy (34.1%), gastrointestinal (23.4 %) and breast cancer (16.1%). 26.1% experienced one or more falls in the past 12 months and 28.9% were worried about falling. Average CARG score is 10.1 (SD = 3.8). 50.4% had an abnormal TUG tests and 23.6% had an abnormal Mini-Cog. In the multivariate logistic regression, CARG score (OR = 1.46 95% CI = 1.30 - 1.65, p = 0.000) was associated with falls in the past 12 months after adjusting for confounders. Further, both abnormal TUG (OR = 4.63 95% CI = 2.12-10.13 p = 0.000) and increased CARG score (OR = 1.17 95% CI = 1.05-1.31 p = 0.005) were associated with FOF. Conclusions: Falls and FOF are common among older cancer patients in our cohort. As the CARG toxicity score found as a major predictor for prior falls, our findings suggest the importance of future toxicity risk-tailored interventions which could potentially lead to the prevention of further falls. We also found that the TUG test and CARG were associated with FOF, which might diminish older cancer patient’s confidence in participating in daily activities. Future research is needed to investigate causal relationship among comprehensive risk factors and the efficacy of tailored interventions.