Systemic Cancer Therapy Research Articles

Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial

Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Taurohyocholic acid acts as a potential predictor of the efficacy of tyrosine kinase inhibitors combined with programmed cell death-1 inhibitors in hepatocellular carcinoma.

Background and aims: Tyrosine kinase inhibitors (TKIs) combined with programmed cell death protein-1 (PD-1) have significantly improved survival in patients with unresectable hepatocellular carcinoma (uHCC), but effective biomarkers to predict treatment efficacy are lacking. Peripheral blood bile acids (BAs) are associated with tumor response to therapy, but their roles in HCC remain unclear. Methods: This retrospective study included HCC patients who received first-line TKIs combined with PD-1 inhibitors treatment (combination therapy) in our clinical center from November 2020 to June 2022. The aim of this study was to analyze the changes in plasma BA profiles before and after treatment in both the responding group (Res group) and the non-responding group (Non-Res group). We aimed to explore the potential role of BAs in predicting the response to combination therapy in HCC patients. Results: Fifty-six patients with HCC who underwent combination therapy were included in this study, with 28 designated as responders (Res group) and 28 as non-responders (Non-Res group). There were differences in plasma BA concentrations between the two groups before systemic therapy. Plasma taurohyocholic acid (THCA) levels in the Res group were significantly lower than those in the Non-Res group. Patients with low levels of THCA exhibited superior median progression-free survival (7.6 vs. 4.9months, p = 0.027) and median overall survival (23.7 vs. 11.6months, p = 0.006) compared to those of patients with high levels of THCA. Conclusion: Peripheral blood BA metabolism is significantly correlated with combination therapy response and survival in patients with HCC. Our findings emphasize the potential of plasma BAs as biomarkers for predicting combination therapy outcomes and offering novel therapeutic targets for modulating responses to systemic cancer therapy.

Potassium imbalances induced by systemic cancer therapy: pathophysiology and potential therapeutic strategies

Potassium imbalances induced by systemic cancer therapy: pathophysiology and potential therapeutic strategies

Systemic therapies for advanced thyroid cancer - an update

Based on phase III clinical studies, four multi-kinase inhibitors (MKI) are approved for the treatment of progressive radioiodine-refractory differentiated thyroid carcinoma (rrDTC) and medullary thyroid carcinoma (MTC) in Germany. Only recently, based on the randomized trial COSMIC-311, Cabozantinib has been approved as a second-line treatment option in advanced rrDTC. As first in-label selective RET-Inhibitor, Selpercatinib showed promising efficacy in advanced MTC (first line) with RET mutations and rrDTC (second line) with RET fusions along with fewer side effects. Changes and new approaches for the treatment of ATC have been summarised in the current ATA guidelines.

Management of Intrahepatic Cholangiocarcinoma: A Narrative Review.

The management of resectable intrahepatic cholangiocarcinoma remains a challenge due to the high risk of recurrence. Numerous clinical trials have identified effective systemic therapies for advanced biliary tract cancer; however, fewer trials have evaluated systemic therapies in the perioperative period. The objective of this review is to summarize the current recommendations regarding the diagnosis, surgical resection, and systemic therapy for anatomically resectable intrahepatic cholangiocarcinoma. Our review demonstrates that surgical resection with microscopic negative margins and lymphadenectomy remains the cornerstone of treatment. High-level evidence regarding specific systemic therapies for use in resectable intrahepatic cholangiocarcinoma remains sparse, as most of the evidence is extrapolated from trials involving heterogeneous tumor populations. Targeted therapies are an evolving practice for intrahepatic cholangiocarcinoma with most evidence coming from phase II trials. Future research is required to evaluate the use of neoadjuvant therapy for patients with resectable and borderline resectable disease.

Exposure-Response Relationships for Pralsetinib in Patients with RET-Altered Thyroid Cancer or RET Fusion-Positive Nonsmall Cell Lung Cancer.

Pralsetinib is a highly potent oral kinase inhibitor of oncogenic RET (rearranged during transfection) fusions and mutations. Pralsetinib received approval from the United States Food and Drug Administration for the treatment of patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), and received accelerated approval for the treatment of patients with RET fusion-positive thyroid cancer. Exposure-response (ER) analyses of efficacy were performed separately in patients with thyroid cancer and in patients with NSCLC, but data for all patients were pooled for the safety analysis. ER models were developed with time-varying exposure; the effect of covariates was also examined. For patients with NSCLC, a higher starting dose was associated with improved progression-free survival (PFS), but this improvement did not correlate with a higher exposure overall. Significant covariates included sex and baseline Eastern Cooperative Oncology Group (ECOG) score. For patients with thyroid cancer, a higher exposure was associated with improved PFS. Significant covariates included prior systemic cancer therapy and ECOG score. For safety, higher exposure was associated with a greater risk of grade≥3 anemia, pneumonia, and lymphopenia. Patients with an ECOG score of ≥1 had an increased risk of grade≥3 pneumonia. Non-White patients had a lower risk of grade≥3 lymphopenia. ER analysis revealed that higher pralsetinib exposure was associated with improved PFS in thyroid cancer, but not in NSCLC. However, a higher starting dose (ie, 400 vs ≤300mg daily) was correlated with better PFS for all indications. Higher exposure was also associated with an increased risk of grade≥3 adverse events (AEs); however, the overall incidence of these events was acceptably low (≤20%). This analysis supports the use of a 400mg starting dose of pralsetinib, allowing for dose reduction in the event of AEs.

Integrative Medicine for Cancer-Related Pain: A Narrative Review

Cancer-related pain (C-RP) is a prevalent and debilitating concern among patients with cancer, with conventional treatments limited in their ability to provide adequate relief, and by the adverse effects associated with their use. Complementary and integrative medicine (CIM) modalities have been shown to be potentially effective and safe for the treatment of pain and related symptoms, when used in conjunction with conventional medications and under medical supervision. An increasing number of oncology centers provide CIM within their conventional supportive and palliative care service, in an “Integrative Oncology” (IO) setting. A large body of clinical research, including systematic reviews and guidelines such as those published in 2022 by the Society for Integrative Oncology (SIO), in collaboration with the American Society for Clinical Oncology (ASCO), support the use of some CIM modalities for C-RP and related concerns. These include acupuncture for general and peri-operative/procedural pain, as well as aromatase inhibitor-associated arthralgia (AIA); reflexology or acupressure for pain during systemic therapy for cancer; hypnosis for procedural pain or pain due to diagnostic workup; and massage for pain experienced by patients during palliative and hospice care. Further research is needed, within both randomized control trials and pragmatic non-controlled studies which are more reflective of the real-life IO setting. This review summarizes the evidence supporting the use of CIM for C-RP; the analgesic mechanism of the modalities presented; and the challenges facing IO researchers, as well as the implementation of the 2022 SIO-ASCO guideline recommendations.

Systemic and tumor-directed therapy for oligorecurrent metastatic prostate cancer (SATURN): Primary endpoint results of a phase II clinical trial.

174 Background: Nearly all men with metastatic hormone-sensitive prostate cancer who receive intermittent androgen deprivation therapy (ADT) will experience a relapse within six months of testosterone recovery. We hypothesized that intensifying intermittent ADT with dual next-generation androgen receptor signaling inhibitors (ARSIs) and adding metastasis-directed stereotactic body radiotherapy (SBRT) would significantly increase the number of men who remain relapse-free six months after testosterone recovery. Methods: Men with 1-5 extrapelvic metastases on prostate-specific membrane antigen (PSMA) PET/CT after initial treatment with definitive-intent radical prostatectomy were enrolled on this phase II study (NCT03902951). Men with visceral metastases were excluded. Patients were treated with 6 months of androgen annihilation therapy (AAT) using leuprolide, abiraterone acetate plus prednisone, and apalutamide. After the first month of AAT, patients received SBRT to all metastases with or without radiotherapy directed to the prostate bed and pelvic lymph nodes. The primary endpoint was the percentage of patients who maintained PSA &lt;0.05 ng/mL six months after testosterone recovery to ≥150 ng/dL, with the study powered to detect an improvement from 1% to 12%. Secondary endpoints included progression-free survival (PFS) starting from AAT initiation and, for patients whose testosterone recovered, eugonadal PFS starting from the time of testosterone recovery. Progression was defined as PSA ≥0.05 ng/mL. Results: 28 men enrolled from March 2021-June 2022. Median follow-up was 20 months (range: 14–27 months). Twenty patients (71.4%) completed six months of ADT with dual ARSIs and SBRT, 5 patients (17.9%) completed ADT with a single ARSI and SBRT, 1 patient (3.6%) completed six months of ADT monotherapy with SBRT, and 2 patients (7.1%) withdrew prematurely. 13/26 patients (50%) maintained PSA &lt;0.05 ng/mL six months after testosterone recovery (95% confidence interval [CI]: 32–67%) compared to the study hypothesis of 12%. Median PFS was 19.3 months (95% CI: 12.8–25.7). 1-year PFS was 69.2%. 21/26 patients (81%) had testosterone recovery at a median of 9.4 months (95% CI: 8.5–10.4) from the start of AAT. Median eugonadal PFS was 11.4 months (95% CI: 4.9–18.0). AAT had 21.4% grade 2 and 21.4% 3 toxicity rates. SBRT had 7.7% grade 2 and no grade 3 toxicity. Conclusions: Half of men with PSMA PET-defined oligorecurrent M1a-b disease who received six months of AAT and metastasis-directed SBRT remained relapse-free six months after testosterone recovery. The regimen was well tolerated, with 90% of patients completing six months of ADT and at least one next-generation ARSI. Further prospective data will evaluate whether dual ARSIs are necessary and the extent to which SBRT with short-course AAT outperforms SBRT with ADT monotherapy in this patient population. Clinical trial information: NCT03902951 .

Systemic and tumor-directed therapy for oligometastatic prostate cancer (SOLAR): A phase II trial for veterans with de novo oligometastatic prostate cancer.

163 Background: Treatment paradigms for oligometastatic castration-sensitive prostate cancer patients are evolving. Molecular imaging improves staging, intensified systemic and primary tumor directed therapy improves survival, metastasis-directed therapy improves local control. The impact of combining these imaging and therapeutic approaches into a planned multimodal treatment strategy is unknown. Here we report a prospective phase II single-arm trial combining local, metastasis-directed, and intensified systemic therapies of limited duration with the objective to durably render Veterans free of progression off therapy. Methods: Veterans with de novo M1a/b prostate cancer and 1-5 radiographically visible M1 lesions underwent radical local treatment, intensified systemic therapy for six months (leuprolide, abiraterone acetate with prednisone, apalutamide), and metastasis-directed stereotactic ablative radiotherapy (SBRT). Radical local therapy was either radical prostatectomy (n=12) with lymph node dissection and post-operative radiotherapy (pT≥3a, N1, or positive margins) or radical radiotherapy (n=12) directed to the prostate, SVs, and pelvic LNs. The primary endpoint was the percentage of patients achieving an undetectable serum PSA (for radical prostatectomy) or &lt;2 ng/mL (for radical radiotherapy) six months after recovery of testosterone to ≥150 ng/dL. Secondary endpoints included time to biochemical progression, time to radiographic progression, time to initiation of alternative antineoplastic therapy, prostate cancer specific survival, health related quality-of-life, safety and tolerability. Results: Twenty-eight patients enrolled and 4 dropped out (3 prior to start of treatment). All were staged by PSMA PET/CT except two (one by Fluciclovine PET/CT, and one by NaF PET/CT, CT, MRI). Twenty-nine percent were M1a, seventy-one percent were M1b. Median follow-up was 30 months (range 20 - 61 months). Mean and median number of M1 metastases were both two. Sixty-two percent completed all planned systemic therapy without dose modification. One did not recover testosterone after 29 months. Twenty-two had &gt;6 months follow-up after testosterone recovery, 19 of 22 (86%) remain free of any progression (primary endpoint). Three had metastatic progression, one poly nodal M1a progression, one multiple bone metastases, one multiple bone and nodal metastases. Grade 2 and 3 toxicities for primary tumor therapy were 46% and 4%; SBRT 0% and 0%; systemic therapy 42% and 4%. There was one Grade 4 toxicity. Conclusions: Although a small trial, a majority of patients with molecular imaging defined de novo oligometastatic prostate cancer treated with primary and metastasis-directed therapy with intensified systemic therapy of limited duration remained free of progression with a recovered testosterone off all active therapy. Clinical trial information: NCT03298087 .

Palliative Care Use Trends, Racial/Ethnic Disparities, and Overall Survival Differences Among Patients With Metastatic Breast Cancer.

Background: Palliative care improves cancer patients' quality of life. Limited research has investigated racial/ethnic disparities in palliative care utilization and its associated survival among metastatic breast cancer (MBC) patients. Objectives: To examine racial/ethnic palliative care use disparities and assess racial/ethnic overall survival differences in MBC patients stratified by palliative care use. Design: A retrospective study of MBC patients from the 2004-2020 National Cancer Database. Measurements: Palliative care was defined as noncurative cancer treatment, including surgery, radiotherapy, systemic therapy, and/or pain management; utilization was coded "yes/no." Racial/ethnic groups included Asian, American Indian or Alaska Native (AIAN), Black, Hawaiian or Other Pacific Islander (HPI), Hispanic, and White. Logistic regression was performed to assess palliative care use disparities. Overall survival was modeled using Cox regression. Results: Of 148,931 patients, the mean age was 62 years; 99% were female; 73% identified as White, 17% as Black, 6% as Hispanic, 3% as Asian, 0.3% as AIAN, and 0.3% as HPI; 42% and 39% had Medicare and private insurance, respectively. Overall, 21% used palliative care, with an increasing utilization rate from 2004 to 2020 (3.6% increase per year, p-trend <0.001). Black (adjusted odds ratio [aOR] = 0.89; 95% confidence interval [CI]: 0.84 to 0.94), Asian (aOR = 0.76; 95% CI: 0.68 to 0.86), and Hispanic (aOR = 0.68; 95% CI: 0.62 to 0.74) patients had a lower likelihood of palliative care utilization than White patients. Among palliative care users, compared with White patients, Black (adjusted hazard ratio [aHR] = 1.14, 95% CI: 1.07 to 1.21) patients had a greater mortality risk, while Asian (aHR = 0.83, 95% CI: 0.71 to 0.97) and Hispanic (aHR = 0.77, 95% CI: 0.69 to 0.87) patients had a lower mortality risk. Conclusions: Palliative care utilization among MBC patients significantly increased but remained suboptimal. Racial/ethnic minority patients were less likely to use palliative care, and Black patients had worse survival, than White patients, suggesting the need for improving palliative care access and ameliorating disparities in MBC patients.

Access to and Timeliness of Lung Cancer Surgery, Radiation Therapy, and Systemic Therapy in New Zealand: A Universal Health Care Context.

Lung cancer is the biggest cancer killer of indigenous peoples worldwide, including Māori people in New Zealand. There is some evidence of disparities in access to lung cancer treatment between Māori and non-Māori patients, but an examination of the depth and breadth of these disparities is needed. Here, we use national-level data to examine disparities in access to surgery, radiation therapy and systemic therapy between Māori and European patients, as well as timing of treatment relative to diagnosis. We included all lung cancer registrations across New Zealand from 2007 to 2019 (N = 27,869) and compared access with treatment and the timing of treatment using national-level inpatient, outpatient, and pharmaceutical records. Māori patients with lung cancer appeared less likely to access surgery than European patients (Māori, 14%; European, 20%; adjusted odds ratio [adj OR], 0.82 [95% CI, 0.73 to 0.92]), including curative surgery (Māori, 10%; European, 16%; adj OR, 0.72 [95% CI, 0.62 to 0.84]). These differences were only partially explained by stage and comorbidity. There were no differences in access to radiation therapy or systemic therapy once adjusted for confounding by age. Although it appeared that there was a longer time from diagnosis to radiation therapy for Māori patients compared with European patients, this difference was small and requires further investigation. Our observation of differences in surgery rates between Māori and European patients with lung cancer who were not explained by stage of disease, tumor type, or comorbidity suggests that Māori patients who may be good candidates for surgery are missing out on this treatment to a greater extent than their European counterparts.

Magnetically guided surgery after primary systemic therapy for breast cancer: implications for enhanced axillary mapping.

Superparamagnetic iron nanoparticles perform comparably to radioisotope ± blue dye for sentinel lymph node detection in breast cancer, even when injected up to 8 weeks before surgery. Using superparamagnetic iron nanoparticles for sentinel lymph node detection after primary systemic therapy, and the maximum time frame of superparamagnetic iron nanoparticle administration have not been investigated. This cohort study included cN0/1-to-ycN0 patients undergoing sentinel lymph node detection or targeted axillary dissection. All patients received superparamagnetic iron nanoparticles either before primary systemic therapy or before surgery, and radioisotope on the day of surgery. For 113 patients analysed, superparamagnetic iron nanoparticles were injected a median of 3 (range 0-248) days before surgery, with a 97.4% detection rate compared with 91.2% for radioisotope (P = 0.057). Concordance for radioisotope was 97.1% and this was not affected by timing of superparamagnetic iron nanoparticle injection (Kendall's tau 0.027; P = 0.746). The median sentinel lymph node yield was 3 (interquartile range (i.q.r.) 2-3) for superparamagnetic iron nanoparticles and 2 (i.q.r. 2-3) for radioisotope (P < 0.001). In targeted axillary dissection, detection was 100% for superparamagnetic iron nanoparticles and 81.8% for radioisotope (P = 0.124). The index node was magnetic in 93.9% and radioactive in 66.7% (P = 0.007), an outcome that was not affected by any factors. For patients with metastases, superparamagnetic iron nanoparticle detection was 100% and radioisotope-based detection was 84.2% (P = 0.083), with superparamagnetic iron nanoparticles detecting more metastatic sentinel lymph nodes (median of 1 (i.q.r. 1-2) for superparamagnetic iron nanoparticles compared with a median of 1 (i.q.r. 0-1) for radioisotope; P = 0.005). Injection before primary systemic therapy is feasible and does not affect concordance with radioisotope. Superparamagnetic iron nanoparticles perform comparably to radioisotope, but detect more sentinel lymph nodes and have a higher rate of detection of metastatic sentinel lymph nodes.

Inhibition of Aurora B kinase (AURKB) enhances the effectiveness of 5-fluorouracil chemotherapy against colorectal cancer cells

Background5-Fluorouracil (5-FU) remains a core component of systemic therapy for colorectal cancer (CRC). However, response rates remain low, and development of therapy resistance is a primary issue. Combinatorial strategies employing a second agent to augment the therapeutic effect of chemotherapy is predicted to reduce the incidence of treatment resistance and increase the durability of response to therapy.MethodsHere, we employed quantitative proteomics approaches to identify novel druggable proteins and molecular pathways that are deregulated in response to 5-FU, which might serve as targets to improve sensitivity to chemotherapy. Drug combinations were evaluated using 2D and 3D CRC cell line models and an ex vivo culture model of a patient-derived tumour.ResultsQuantitative proteomics identified upregulation of the mitosis-associated protein Aurora B (AURKB), within a network of upregulated proteins, in response to a 24 h 5-FU treatment. In CRC cell lines, AURKB inhibition with the dihydrogen phosphate prodrug AZD1152, markedly improved the potency of 5-FU in 2D and 3D in vitro CRC models. Sequential treatment with 5-FU then AZD1152 also enhanced the response of a patient-derived CRC cells to 5-FU in ex vivo cultures.ConclusionsAURKB inhibition may be a rational approach to augment the effectiveness of 5-FU chemotherapy in CRC.

Systemic therapy of prostate cancer in elderly patients

Systemic therapy of prostate cancer in elderly patients

Geographic and sociodemographic access to systemic anticancer therapies for secondary breast cancer: a systematic review

BackgroundThe review aimed to investigate geographic and sociodemographic factors associated with receipt of systemic anticancer therapies (SACT) for women with secondary (metastatic) breast cancer (SBC).MethodsIncluded studies reported geographic and sociodemographic factors associated with receipt of treatment with SACT for women > 18 years with an SBC diagnosis. Information sources searched were Ovid CINAHL, Ovid MEDLINE, Ovid Embase and Ovid PsychINFO. Assessment of methodological quality was undertaken using the Joanna Briggs Institute method. Findings were synthesised using a narrative synthesis approach.ResultsNineteen studies published between 2009 and 2023 were included in the review. Overall methodological quality was assessed as low to moderate. Outcomes were reported for treatment receipt and time to treatment. Overall treatment receipt ranged from 4% for immunotherapy treatment in one study to 83% for systemic anticancer therapies (unspecified). Time to treatment ranged from median 54 days to 95 days with 81% of patients who received treatment < 60 days.Younger women, women of White origin, and those women with a higher socioeconomic status had an increased likelihood of timely treatment receipt. Treatment receipt varied by geographical region, and place of care was associated with variation in timely receipt of treatment with women treated at teaching, research and private institutions being more likely to receive treatment in a timely manner.ConclusionsTreatment receipt varied depending upon type of SACT. A number of factors were associated with treatment receipt. Barriers included older age, non-White race, lower socioeconomic status, significant comorbidities, hospital setting and geographical location. Findings should however be interpreted with caution given the limitations in overall methodological quality of included studies and significant heterogeneity in measures of exposure and outcome. Generalisability was limited due to included study populations.Findings have practical implications for the development and piloting of targeted interventions to address specific barriers in a socioculturally sensitive manner. Addressing geographical variation and place of care may require intervention at a commissioning policy level. Further qualitative research is required to understand the experience and of women and clinicians.Systematic review registrationPROSPERO CRD42020196490

Nomogram to predict risk of early mortality following definitive or adjuvant radiation and systemic therapy for head and neck cancer

Purpose/ObjectivesWe sought to create nomograms to predict individual risk of early mortality, which can identify patients who require interventions to prevent early death. MethodsWe included patients in the National Cancer Database with non-metastatic squamous cell carcinoma of the head and neck who received radiation and systemic therapy between 2004 and 2017 in the definitive or adjuvant setting. Early mortality was defined as any death less than 90 days after starting radiation. Multivariable logistic regression was used to assess the relationship between covariates and early mortality. Nomograms to predict the risk of early death were created for both the definitive and adjuvant settings. ResultsAmong 84,563 patients in the definitive group and 18,514 patients in the adjuvant group, rates of early mortality were 3.5 % (95 % CI 3.4–3.7 %) and 2.2 %, (95 % CI 1.9–2.4 %), respectively. Patients above the age of 70 had an early mortality rate of 7.8 % (95 % CI 7.3–8.2 %) in the definitive group and 4.4 % (95 % CI 3.6–5.4 %) in the adjuvant group. In the multivariable analysis, age, comorbidity, T and N category, and tumor site were associated with early mortality in both cohorts (p < 0.05 for all). Nomograms including age, comorbidity, T and N category and tumor site performed better than age alone at predicting early mortality (AUC for definitive group: 0.70 vs 0.66; AUC for adjuvant group: 0.71 vs 0.61). ConclusionNomograms including age, comorbidity, T and N category and tumor site were developed to predict the risk of early death following definitive or adjuvant chemoradiation.

Upfront Versus Delayed Systemic Therapy in Patients With Oligometastatic Cancer Treated With SABR in the Phase 2 SABR-5 Trial

The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P = .005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P = .65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P < .001). Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach.

Patients' perception of the benefits of palliative systemic therapy for advanced cancer.

Patients with advanced cancer who misunderstand their prognosis and chance of cure tend to overestimate the likely benefits of palliative systemic therapy. To determine patient perceptions of palliative systemic therapy benefits in advanced cancer. We surveyed 104 outpatients with advanced cancer receiving systemic anticancer therapy and their treating oncologists. Patients recorded their understanding of treatment impact on chance of cure and symptoms. Life expectancy was estimated by patients and oncologists. A visual analogue scale (0-10) was used to record how patients and oncologists valued quality of life (QOL) and length of life (LOL) (<4 QOL most important; 4-7 QOL and LOL equal; >7 LOL most important). Patient-oncologist discordance was defined as a ≥4-point difference. The main reasons patients selected for receiving treatment were to live longer (54%) and cure their cancer (36%). Most patients reported treatment was very/somewhat likely to prolong life (84%) and improve symptoms (76%), whereas 20% reported treatment was very/somewhat likely to cure their cancer. 42% of patients selected a timeframe for life expectancy (choice of four timeframes between <1 year and ≥5 years); of these, 62% selected a longer timeframe than their oncologist. When making treatment decisions, 71% of patients (52% of oncologists) valued QOL and LOL equally. Patient-oncologist discordance was 21%, mostly because of oncologists valuing QOL more than their patients (70%). At least 20% of patients receiving systemic therapy for advanced cancer reported an expectation of cure. Most patients and oncologists value QOL and LOL equally when making treatment decisions.

Revolutionizing colon cancer therapy by site-specific 5-fluorouracil delivery with novel stimuli-responsive mucoadhesive hydrogel: Optimization via response surface methodology

5-fluorouracil (FU) is the key option of systemic therapy for advanced metastatic colon cancer but has a cytotoxic impact on normal cells after intravenous administration therefore the primary goal of this research was to fabricate a unique oral site-specific mucoadhesive delivery technique for FU to reach the colon and improving the targeting effectiveness of FU to colon. In the present research, we investigate the novel utilization of developed carboxymethyl cellulose/polyvinylpyrrolidone-grafted-poly(acrylic acid) based hydrogel as a potential carrier for FU administration. The utilization of such novel hydrogels as potential mucoadhesive and swelling behaviour candidates, carriers of FU for colon cancer, as well as the in-vitro evaluations of FU-release, Fourier transform infrared spectroscopy (FTIR), 13C Nuclear magnetic spectroscopy (13C NMR), X-ray diffraction (XRD), thermal analysis, average molecular weight between crosslinks (Mc), cross-link density, in addition to cytotoxicity analysis, hemocompatibility evaluation and acute oral toxicity analysis, were carried out. Notably, over the initial 36 h of dissolution, FU % cumulative release from CMC/PVP-g-poly (AA) hydrogel ranges from 2.62 % to 6.60 % at 1.2 pH, 7.23 %–11.35 % at 6.8 pH, and 85.48 %–99.63 % at 7.4 pH, respectively. Its thermal stability has been demonstrated by TGA and DSC. The FTIR, 13C NMR and XRD have verified the molecular-level entrapment of FU inside the designed hydrogel. Scanning Electron Microscopy (SEM) results showed that the produced hydrogel had an irregular along with porous surface. The degree of a hydrogel's swelling and crosslink density were found to be negatively correlated with each other, whereas Mc was directly linked with the swelling of accomplished hydrogel. The developed hydrogel with the highest carboxymethyl cellulose (CMC) content demonstrated 147 min of mucoadhesion with colonic mucosal lining. Cytotoxicity analysis, hemocompatibility evaluation and acute oral toxicity testing confirmed the biocompatibility of the fabricated hydrogel and indicated their potential for safe as well as site-specific sustained FU transport as well as being used as a valuable asset of therapeutic agents for colon cancer treatment.

Retracted: Long Noncoding RNAs: New Regulators of Resistance to Systemic Therapies for Gastric Cancer.

[This retracts the article DOI: 10.1155/2021/8853269.].