Curr. Oncol., Volume 29, Issue 10 (October 2022) – 104 articles

Purpose: The purpose of this study was to investigate the prognostic differences between patients with small-cell lung cancer (SCLC) with different chemosensitivity to first-line chemotherapy who developed brain metastasis (BM) as the first site of progression. Methods: Patients with a BM after first-line treatment in the Tianjin Cancer Hospital were retrospectively analyzed. According to the time-free interval (TFI) between the completion of first-line chemotherapy and the onset of the BM, the patients were divided into the chemo-sensitive group (TFI ≥ 90 days, n = 145) and the chemo-resistant group (TFI < 90 days, n = 97). The survival time, which was calculated from the diagnosis of the BM, was analyzed after the onset of brain metastasis (BM-OS). Survival curves were plotted using the Kaplan–Meier method, and differences between groups were compared using the log-rank test. Results: In total, the median BM-OS was 8.4 months. The median BM-OS in the chemo-sensitive group was 8.8 months, and it was 8.0 months in the chemo-resistant group (p = 0.538). In patients without extracranial progression (n = 193), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 9.4 months and 9.7 months, respectively (p = 0.947). In patients with extracranial progression (n = 49), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 5.4 months and 4.2 months, respectively (p = 0.161). Conclusions: After the development of a BM as the first site of progression following chemotherapy in patients with SCLC, the prognosis of chemo-sensitive patients was not necessarily superior to chemo-resistant patients, especially in patients without extracranial progression. Full article

Few studies have focused on the link between active surveillance (AS) and Gleason score upgrade (GSU) and its impact on the prognosis of patients with prostate cancer (PCa). This study aimed to analyze the effect of AS duration on GSU and prognostic value based on risk stratification. All eligible patients were risk-stratified according to AUA guidelines into low-risk (LR), favorable intermediate-risk (FIR), and unfavorable intermediate-risk (UIR) PCa. Within the Surveillance, Epidemiology, and End Results Program (SEER) database, 28,368 LR, 27,243 FIR, and 12,210 UIR PCa patients were included. The relationship between AS duration and GSU was identified with univariate and multivariate logistic regression. Discrimination according to risk stratification of AS duration and GSU was tested by Kaplan–Meier analysis and competing risk regression models. The proportion of patients who chose AS was the highest among LR PCa (3434, 12.1%), while the proportion in UIR PCa was the lowest (887, 7.3%). The AS duration was only associated with GSU in LR PCa, with a high Gleason score (GS) at diagnosis being a strong predictor of GSU for FIR and UIR PCa. Kaplan–Meier analysis indicated that long-term surveillance only made a significant difference in prognosis in UIR PCa. The competing risk analysis indicated that once GS was upgraded to 8 or above, the prognosis in each group was significantly worse. AS is recommended for LR and FIR PCa until GS is upgraded to 8, but AS may not be suitable for some UIR PCa patients. Full article

ICI therapy has greatly improved patient outcomes in melanoma, but at the cost of immune-related adverse events (irAEs). Data on the chronicity of irAEs, especially in real-world settings, are currently limited. We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥ 6 months), transient (resolution over a period < 6 months), or no irAEs. A total of 283 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, fifteen (9.3%) experienced long-term irAEs as their longest-lasting toxicity, thirty-four (21.1%) developed transient irAEs only, and forty-six (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (36.0%) or skin-related (32.4%). Grade 3–4 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still requiring treatment for long-term or permanent irAEs 6 months or more following the completion of ICI therapy, including twenty-four patients on thyroid hormone replacement and twenty-two on oral steroids. ICI treatment was temporarily interrupted for 64 (22.6%) irAEs and permanently discontinued due to irAEs in 38 patients (13.6% of irAEs, 23.6% of patients); additionally, 4 (2.5%) patients died of irAEs. Our findings show that ICI treatment in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients, which should therefore be discussed when obtaining consent for treatment. Full article

Background: Sleep–wake disturbance is prevalent in patients with liver cancer, but there is no direct evidence of its association and related biological mechanisms. Our study was to assess quality of sleep and to describe prevalence of sleep disturbances in patients with different etiologies of liver cancer, especially to explore whether sleep quality influences immune factors. Methods: A total of 210 patients with liver cancer from August 2015 to December 2015 were randomly divided into two groups including HBV cirrhosis and non-HBV cirrhosis. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate their sleep quality, and then 202 patients enrolled in this study were divided into two groups according to their PSQI scores: PSQI ≤ 5 and PSQI > 5. The association between sleep disturbances and immune factors was analyzed by logistic regression models. Results: A total of 56.9% of liver cancer patients experienced poor sleep quality (PSQI > 5). The prevalence of sleep disturbances was significantly higher in patients with liver cancer of non-hepatitis B virus (HBV) cirrhosis than with that evolving from HBV cirrhosis (66.7% vs. 50%, p = 0.018). In non-HBV cirrhosis liver cancer patients, the PSQI > 5 group had a higher percentage of CD3⁺ T cells (71.06 ± 11.07 vs. 63.96 ± 14.18, p = 0.014) and lower natural killer (NK) cells (14.67 ± 9.65 vs. 20.5 ± 10.77, p = 0.014) compared with patients with PSQI ≤ 5. Logistic regression further confirmed that liver cancer patients without HBV cirrhosis are more prone to experience poor sleep with increased CD3⁺ T cells (OR = 1.07, 95% CI = 1.01–1.13, p = 0.030) and decreased NK cells (OR = 0.92, 95% CI = 0.85–0.98, p = 0.014). Our results indicate that increased CD3⁺ T cells and decreased NK cells are both associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis. Conclusions: Most liver cancer patients suffer from sleep disturbances, especially evolving from non-HBV cirrhosis. A rise in CD3⁺ T cells and a reduction in NK cells are associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis. Full article

Palliative radiotherapy (PRT) is known to be effective in relieving cancer related symptoms. However, many studies and clinical practice show several barriers hindering its use and worsening the quality of patient support during PRT. Various solutions were proposed to overcome these barriers: training on PRT for supportive and palliative care specialists and training on palliative care for radiation oncologists, and introduction of pathways and organizational models specifically dedicated to PRT. Evidence on innovative organizational models and mutual training experiences is few and sparse. Therefore, the aim of this literature review is to present a quick summary of the information available on improving the PRT quality through training, new pathways, and innovative organizational models. The majority of studies on the integration of PRT with other palliative and supportive therapies present low levels of evidence being mostly retrospective analyses. However, it should be emphasized that all reports uniformly showed advantages coming from the integration of PRT with supportive therapies. To actively participate in the integration of PRT and palliative care, providing comprehensive support to the needs of patients with advanced cancer, radiation oncologists should not only plan PRT but also: (i) assess and manage symptoms and stress, (ii) rapidly refer patients to specialists in management of more complex symptoms, and (iii) participate in multidisciplinary palliative care teams. To this end, improved education in palliative care both in residency schools and during professional life through continuous medical education is clearly needed. In particular, effective training is needed for radiotherapy residents to enable them to provide patients with comprehensive palliative care. Therefore, formal teaching of adequate duration, interactive teaching methods, attendance in palliative care services, and education in advanced palliative care should be planned in post-graduated schools of radiotherapy. Full article

Cholangiocarcinoma (CCA) is the second most frequent primary liver cancer, following hepatocellular carcinoma (HCC). Progress in the molecular understanding of CCA has led to the development of several agents, including FGFR inhibitors, such as pemigatinib, whose approval has marked a new era in this hepatobiliary malignancy. However, a number of questions remain unanswered, including the development of secondary resistance and the role of combination therapies, including FGFR inhibitors. Herein, we specifically focus on the current challenges and future research directions of pemigatinib use in CCA patients. Full article

Background: While radiotherapy has been studied in the treatment of locally advanced pancreatic ductal adenocarcinoma (PDAC), few studies have analyzed the effects of radiotherapy on PDAC in patients with liver metastases. This study aimed to determine whether PDAC patients with liver metastases have improved survival after radiotherapy treatment. Methods: The data of 8535 patients who were diagnosed with PDAC with liver metastases between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis and Cox proportional hazards regression analysis of cancer-specific mortality and overall survival were performed, and propensity score matching (PSM) was used to reduce selection bias. Results: After PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the radiotherapy group were longer than those in the nonradiotherapy group (OS: 6 months vs. 4 months; mCSS: 6 months vs. 5 months, both p < 0.05), respectively. The multivariate analysis showed that cancer-specific mortality rates were higher in the nonradiotherapy group than in the radiotherapy group (HR: 1.174, 95% CI: 1.035–1.333, p = 0.013). The Cox regression analysis according to subgroups showed that the survival benefits (OS and CSS) of radiotherapy were more significant in patients with tumor sizes greater than 4 cm (both p < 0.05). Conclusions: PDAC patients with liver metastases, particularly those with tumor sizes greater than 4 cm, have improved cancer-specific survival (CSS) rates after receiving radiotherapy. Full article

Introduction: Patients with advanced-stage non-small cell lung cancer (NSCLC) may benefit from a short time-to-treatment (TTT). Predictive biomarker testing is performed prior to treatment, as recommended by various international expert consensus bodies. Genetic testing is more time-intensive than immunohistochemistry (IHC) and commonly contributes to prolonged TTT. For epidermal growth factor receptor-positive patients (EGFR+), further genetic testing may not be required due to the mutual exclusivity of actionable mutations. Methods: The trial cohort (N = 238) received both BC Cancer NGS panel (Oncopanel) and Idylla EGFR testing. Data were also collected for a control cohort (N = 220) that received Oncopanel testing. For each patient, the time that the lab received the sample, the time taken to report the NGS and Idylla tests, the time of first treatment, and the final treatment regimen were recorded. Results: A concordance frequency of 98.7% (232/235) was observed between the Idylla and NGS panel. The lab turnaround time (TAT) was faster for the Idylla test by an average of 12.4 days (N = 235, p < 0.01). Overall, the average TTT in the trial cohort (N = 114) was 10.1 days faster (p < 0.05) than the control (N = 114), leading to a 25% reduction in TTT. For patients treated based on EGFR positivity, the mean TTT was 16.8 days faster (p < 0.05) in the trial cohort (N = 33) than the control cohort (N = 28), leading to a 48% reduction in TTT. Conclusion: Using the Idylla EGFR test as part of the molecular testing repertoire in advanced-stage NSCLC patients could significantly reduce TTT. Full article

Aim. The present study aimed to assess the existing data about Primary Adrenal Lymphoma (PAL) evaluated with FDG PET and to describe a small monocentric series of cases. A systematic analysis (from 2010 to 2022) was made by using PubMed and Web of Science databases reporting data about the role of FDG PET/CT in patients with suspicious or known adrenal lymphoma. The quality of the papers was assessed by using QUADAS-2 criteria. Moreover, from a single institutional collection between 2010 and 2021, data from patients affected by adrenal lymphoma and undergoing contrast-enhanced compute tomography (ceCT)/magnetic resonance (MR) and FDG PET/CT or PET/MR were retrieved and singularly described. Seventy-eight papers were available from PubMed and 25 from Web of Science. Forty-seven (Nr. 47) Patients were studied, most of them in the initial staging of disease (n = 42; 90%). Only in one paper, the scan was made before and after therapy. The selected clinical cases were relative to the initial staging of disease, the restaging, and the evaluation of response to therapy. PET/CT and PET/MR always showed a high FDG uptake in the primary adrenal lesions and in metastatic sites. Moreover, PET metrics, such as maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV), were elevated in all primary adrenal lesions. In conclusions, FDG PET either coupled with CT or MRI can be useful in staging, restaging, and for the evaluation of treatment response in patients affected by PAL Full article

Boron neutron capture therapy (BNCT) is a binary modality that is used to treat a variety of malignancies, using neutrons to irradiate boron-10 (¹⁰B) nuclei that have entered tumor cells to produce highly linear energy transfer (LET) alpha particles and recoil ⁷Li nuclei (¹⁰B [n, α] ⁷Li). Therefore, the most important part in BNCT is to selectively deliver a large number of ¹⁰B to tumor cells and only a small amount to normal tissue. So far, BNCT has been used in more than 2000 cases worldwide, and the efficacy of BNCT in the treatment of head and neck cancer, malignant meningioma, melanoma and hepatocellular carcinoma has been confirmed. We collected and collated clinical studies of second-generation boron delivery agents. The combination of different drugs, the mode of administration, and the combination of multiple treatments have an important impact on patient survival. We summarized the critical issues that must be addressed, with the hope that the next generation of boron delivery agents will overcome these challenges. Full article

Aims: We report the mature toxicity data of a phase II non-randomized trial on the use of SBRT for lung and liver oligometastases. Methods: Oligometastatic patients from breast cancer were treated with SBRT for up to five lung and/or liver lesions. Inclusion criteria were: age > 18 years, ECOG 0–2, diagnosis of breast cancer, less than five lung/liver lesions (with a maximum diameter <5 cm), metastatic disease confined to the lungs and liver or extrapulmonary or extrahepatic disease stable or responding to systemic therapy. Various dose–fractionation schedules were used. Then, a 4D-CT scan and FDG-CTPET were acquired for simulation and fused for target definition. Results: From 2015 to 2021, 64 patients and a total of 90 lesions were irradiated. Treatment was well tolerated, with no G 3–4 toxicities. No grade ≥3 toxicities were registered and the coprimary endpoint of the study was met. Median follow-up was 19.4 months (range 2.6–73.1). Conclusions: The co-primary endpoint of this phase II trial was met, showing excellent tolerability of SBRT for lung and liver oligometastatic in breast cancer patients. Until efficacy data will mature with longer follow-up, SBRT should be regarded as an opportunity for oligometastatic breast cancer patients. Full article

En bloc resection consists in the surgical removal of a vertebral tumor in a single piece with a sufficient margin, to improve survival and reduce recurrence rate. This procedure is technically demanding and correlates with a high complication rate. The purpose of this study is to investigate the risk factors for complications in en bloc resection and evaluate if benefits overcome the risks in term of overall survival. We retrospectively analyzed prospectively collected data of patients treated with en bloc resection between 1980 and 2021. Complications were classified according to SAVES-V2. Overall Survival was estimated using Kaplan-Meier method. A total of 149 patients out of 298 (50%) suffered from at least one complication. Moreover, 220 adverse events were collected (67 intraoperative, 82 early post-operative, 71 late post-operative), 54% of these were classified as grade 3 (in a severity scale from 1 to 6). Ten years overall survival was 67% (95% CI 59–74). The occurrence of relapses was associated to an increased risk of mortality with OR 3.4 (95% CI 2.1–5.5), while complications did not affect the overall survival. Despite a high complication rate, en bloc resection allows for a better control of disease and should be performed in selected patients by specialized surgeons. Full article

Background: Stereotactic ablative body radiotherapy (SABR) is one of the treatment options for oligometastatic renal cell carcinoma (RCC) but is limited by a lack of data to evaluate high-dose SABR to all/multiple sites. Objective: This study retrospectively investigated the efficacy and prognostic factors of high-dose SABR for oligometastatic RCC patients. Design, setting, and participants: Patients with oligometastatic RCC on systemic therapy were retrospectively collected. Intervention(s): All patients were treated with SABR (40–50 Gy/5 fractions) for small tumors or partial-SABR (tumor center boosted with 6–8 Gy/3–5 fractions with 50–60 Gy/20–25 fractions to the whole tumor volume) for bulky tumors or tumors adjacent to critical organs. Outcome measurements and statistical analysis: Progression-free survival (PFS) and overall survival (OS) were calculated. Results and limitations: In total, 35 patients were enrolled, of which 88.5% had intermediate- or high-risk disease, with 60% on second- to fourth-line systemic therapy. The median follow-up time was 17 months. The median PFS and OS times were 11.3 and 29.7 months, respectively. Univariate analysis showed that an OS benefit was found in patients who received radiation before tyrosine kinase inhibitor (TKI) failure (p = 0.006) and where there was a short time interval (<six months) from being diagnosed with metastatic disease to undergoing radiotherapy (p = 0.046). Similar results were also found in PFS in patients who received radiation before TKI failure (p = 0.049) or within eight months (p = 0.047). There were certain differences in PFS (p = 0.033) between patients receiving radiotherapy with all lesions and those with selected tumors. In multivariate analysis, OS benefits were found in patients who received radiotherapy before TKI failure (p = 0.028). The limitations of this study include its retrospective design and the small patient cohort. Conclusions: The early use of high-dose SABR to multi-lesions may improve survival. Partial-SABR for bulky lesions close to critical organs could be safely and effectively applied under certain circumstances. Full article

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and is the leading cause of cancer-related death. Despite advances in chemotherapy and immunotherapy, the prognosis for advanced patients remains poor. The discovery of oncogenic driver mutations, such as anaplastic lymphoma kinase (ALK) mutations, means that a subset of patients has opportunities for targeted therapy. With the improvement of genetic testing coverage, more and more ALK fusion subtypes and ALK partners have been discovered, and more than 90 rare ALK fusion subtypes have been found in NSCLC. However, unlike the common fusion, echinoderm microtubule-associated protein-like 4 (EML4)-ALK, some rare ALK fusions such as striatin (STRN)-ALK and huntingtin interacting protein 1 (HIP1)-ALK, etc., the large-scale clinical data related to its efficacy are still immature. The clinical application of ALK-tyrosine kinase inhibitors (ALK-TKIs) mainly depends on the positivity of the ALK gene, regardless of the molecular characteristics of the fusion partner. Recent clinical studies in the ALK-positive NSCLC population have demonstrated differences in progression-free survival (PFS) among patients based on different ALK fusion subtypes. This article will introduce the biological characteristics of ALK fusion kinase and common detection methods of ALK fusion and focus on summarizing the differential responses of several rare ALK fusions to ALK-TKIs, and propose corresponding treatment strategies, so as to better guide the application of ALK-TKIs in rare ALK fusion population. Full article

Small cell carcinoma of the ovary (SCCO) is a rare type of ovarian cancer with high aggressiveness. The optimal treatment modality remains elusive. This study aims to comprehensively investigate the survival impact of clinical characteristics and treatments including lymphadenectomy in SCCO. A retrospective cohort study was performed and included patients from the Surveillance, Epidemiology, and End Results (SEER) database. Data collected included demographics, therapeutic details, and pathologic characteristics. Propensity-score matching analysis (PSM) was carried out to balance baseline variables between SCCO and non-SCCO. Cox regression, Kaplan–Meier, and stratified analyses were conducted before and after PSM. After filtering, 80 records on SCCO and 39,662 records on non-SSCO were obtained. Patients with SCCO were more prone to present unilateral tumor (57.6% and 85.0%, p < 0.001), larger tumor size (>15 cm: 9.5% and 32.5%; 10–15 cm: 13.2% vs. 22.5%, p < 0.001), younger age (59.1 ± 14.91 vs. 37.2 ± 19.05; p < 0.001), single status (17.0% vs. 45.0%; p < 0.001), single malignant tumor in a lifetime (76.1% vs. 87.5%; p = 0.0244), and pathologic grade IV diseases (14.5% vs. 40.0%; p < 0.001) compared with non-SCCO. After balancing the baseline clinical characteristics with a 1:4 ratio PSM, a total of matched 72 patients with SCCO and 254 patients with non-SCCO were identified. The survival rate of SCCO was distinctly inferior to non-SCCO, particularly in FIGO I, II, and III stages. Lymphadenectomy was performed in 37 (51.39%) SCCO patients, of whom 12 (32.43%) were found to have pathologically positive lymph nodes. Lymphadenectomy was linked to favorable overall survival in SCCO, particularly in the advanced stage, and was also an independent prognostic factor, whereas lymphadenectomy did not reveal an edge in matched non-SCCO. There was a pronounced survival benefit for SCCO when at least 10 or more nodes were resected. Lymphadenectomy in a non-stage-dependent way should be considered and deserves further clinical validation to promote the overall survival in SCCO. Full article

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer. The standard curative treatment is surgical resection, but the treatment of locally advanced and metastatic disease apart from radiotherapy is currently based on cemiplimab. Cemiplimab has demonstrated efficacy in the treatment of advanced and metastatic cSCC in clinical trials, although real-world data are still limited. We present four cases of cSCC, which showed a tremendous response to cemiplimab—one patient achieved complete response and three of them achieved partial response. Immunotherapy with cemiplimab, a recently approved PD1 inhibitor, is an important addition to the cutaneous oncology therapeutic options that may be considered in patients with advanced disease not amenable to surgery or radiotherapy. In all four cases, the patients postponed visits to the doctor because of the fear of SARS-CoV-2 infection or for administrative and organizational reasons declared difficult access to doctors caused by the pandemic. Full article

Introduction: Breast cancer is the most common form of cancerous disease worldwide. Its treatment leads to a variety of physiological and psychological side effects. This review investigates the question of how mindfulness-based stress reduction (MBSR), a stress management program, can influence the quality of life, anxiety, and depression of women diagnosed with breast cancer. Methods: A systematic literature search was conducted in PubMed/MEDLINE and Cochrane Library. Screening by title, abstract and full text was performed, whereby only those articles were included that fit the inclusion criteria. A risk of bias assessment was performed for each included study. Results: Overall, six studies were included, but not every study investigated all three outcomes. Two studies found positive impacts on quality of life, whereas three did not find a positive correlation between the intervention and quality of life. Four out of six studies found a positive relation between MBSR and anxiety scores, but only half of the included studies found positive results for the interaction between MBSR and depression scores. Conclusion: Published data suggest that anxiety can be positively influenced by MBSR, which can be used to improve the psychological care of breast cancer patients, both during and after treatment. However, further studies with larger patient numbers and longer observation periods should be conducted in order to elucidate the full potential of MSBR on important areas such as depression and quality of life. Full article

Li-Fraumeni-syndrome (LFS) is a rare, highly penetrant cancer predisposition syndrome (CPS) caused by pathogenic variants (PVs) in TP53. Physical activity (PA) and a Mediterranean diet lead to cancer reduction or survival benefits and increased quality of life (QoL), but this is yet unstudied among LFS. TP53 PV carriers (PVC) and their relatives were questioned on dietary patterns (Mediterranean Diet Adherence Screener), PA (Freiburg Questionnaire), QoL (Short-form-Health-Survey-12), smoking, alcohol consumption and perception of cancer risk in a German bi-centric study from March 2020–June 2021. The study enrolled 70 PVC and 43 relatives. Women compared to men (6.49 vs. 5.38, p = 0.005) and PVC to relatives (6.59 vs. 5.51; p = 0.006) showed a healthier diet, associated with participation in surveillance (p = 0.04) and education (diet p = 0.02 smoking p = 0.0003). Women smoked less (2.91 vs. 5.91 packyears; p = 0.03), psychological well-being was higher among men (SF-12: males 48.06 vs. females 41.94; p = 0.004). PVC rated their own cancer risk statistically higher than relatives (72% vs. 38%, p < 0.001) however, cancer risk of the general population was rated lower (38% vs. 70%, p < 0.001). A relative’s cancer-related death increased the estimated personal cancer risk (p = 0.01). The possibilities of reducing cancer through self-determined health behavior among PVC and relatives has not yet been exhausted. Educating families with a CPS on cancer-preventive behavior requires further investigation with regard to acceptance and real-life implementation. Full article

Limb preservation with megaendoprosthesis in adolescents and young adults (AYA) with bone tumors is associated with functional limitations and gait abnormalities. The proGAIT trial evaluated the effectiveness of an exercise program on gait function and quality of life, functional scales (MSTS, TESS), functional mobility, and fatigue as secondary outcomes. Eleven AYA survivors of malignant osteosarcoma with a tumor endoprosthesis around the knee (mean age: 26.6 (±8.4) years) were randomized into an intervention group receiving an 8-week exercise program or into a control group. Gait function was assessed via 3D motion capture and analyzed using the Gait Profile Score (GPS) and the Gait Deviation Index (GDI). GDI and GPS scores of participants suggest deviations from a healthy reference group. The exercise intervention had small-to-medium positive effects on gait score GDI |d| = 0.50 (unaffected leg), |d| = 0.24 (affected leg), subjective functional scores TESS |d| = 0.74 and MSTS |d| = 0.49, and functional tests TUG and TUDS |d| = 0.61 and |d| = 0.52. None of these changes showed statistical significance. Promising intervention effects suggest that regular exercise could improve lower limb function and follow-up care for survivors; however, a powered RCT as a follow-up project needs to confirm the pilot findings. Full article

Introduction: Androgen receptor pathway inhibitors (ARPIs) have been increasingly offered to older patients with prostate cancer (PC). However, prognostic factors relevant to their outcome with ARPIs are still little investigated. Methods and Materials: The Meet-URO network ADHERE was a prospective multicentre observational cohort study evaluating and monitoring adherence to ARPIs metastatic castrate-resistant PC (mCRPC) patients aged ≥70. Cox regression univariable and multivariable analyses for radiographic progression-free (rPFS) and overall survival (OS) were performed. Unsupervised median values and literature-based thresholds where available were used as cut-offs for quantitative variables. Results: Overall, 234 patients were enrolled with a median age of 78 years (73–82); 86 were treated with abiraterone (ABI) and 148 with enzalutamide (ENZ). With a median follow-up of 15.4 months (mo.), the median rPFS was 26.0 mo. (95% CI, 22.8–29.3) and OS 48.8 mo. (95% CI, 36.8–60.8). At the MVA, independent prognostic factors for both worse rPFS and OS were Geriatric G8 assessment ≤ 14 (p < 0.001 and p = 0.004) and PSA decline ≥50% (p < 0.001 for both); time to castration resistance ≥ 31 mo. and setting of treatment (i.e., post-ABI/ENZ) for rPFS only (p < 0.001 and p = 0.01, respectively); age ≥78 years for OS only (p = 0.008). Conclusions: Baseline G8 screening is recommended for mCRPC patients aged ≥70 to optimise ARPIs in vulnerable individuals, including early introduction of palliative care. Full article

Due to the ramping down of cancer surgery in early pandemic, many newly diagnosed patients received other treatments first. We aimed to quantify the pandemic-related shift in rate of surgery following chemotherapy. This is a retrospective population-based cohort study involving adults diagnosed with cancer between 3 January 2016 and 7 November 2020 in Ontario, Canada who received chemotherapy as first treatment within 6-months of diagnosis. Competing-risks regression models with interaction effects were used to quantify the association between COVID-19 period (receiving a cancer diagnosis before or on/after 15 March 2020) and receipt of surgical reSection 9-months after first chemotherapy. Among 51,653 patients, 8.5% (n = 19,558) of them ultimately underwent surgery 9-months after chemotherapy initiation. Receipt of surgery was higher during the pandemic than before (sHR 1.07, 95% CI 1.02–1.13). Material deprivation was independently associated with lower receipt of surgery (least vs. most deprived quintile: sHR 1.11, 95% CI 1.04–1.17), but did not change with the pandemic. The surgical rate increase was most pronounced for breast cancer (sHR 1.13, 95% CI 1.06–1.20). These pandemic-related shifts in cancer treatment requires further evaluations to understand the long-term consequences. Persistent material deprivation-related inequity in cancer surgical access needs to be addressed. Full article

Anaplastic thyroid carcinoma (ATC) are highly aggressive malignant tumors with poor overall prognosis despite multimodal therapy. As ATC are extremely rare, no randomized controlled study has been published for metastatic disease. Thyrosine kinase inhibitors, especially lenvatinib and immune checkpoint inhibitors such as pembrolizumab, are emerging drugs for ATC. Few studies have reported the efficacity of pembrolizumab and lenvatinib association, resulting in its frequent off-label use. In this review, we discuss rationale efficacy and safety evidence for the association of lenvatinib and pembrolizumab in ATC. First, we discuss preclinical rationale for pembrolizumab monotherapy, lenvatinib monotherapy and synergistic action of pembrolizumab and lenvatinib in the metastatic setting. We also discuss clinical evidence for immunotherapy and pembrolizumab in ATC through the analysis of studies evaluating immunotherapy, lenvatinib and pembrolizumab lenvatinib association in ATC. In addition, we discuss the safety of this association and potential predictive biomarkers of efficiency. Full article

Perspectives of cancer survivors, caregivers, and social workers as key stakeholders on the clinical management of financial toxicity (FT) are critical to identify opportunities for better FT management. Semi-structured interviews (cancer survivors, caregivers) and a focus group (social workers) were undertaken using purposive sampling at a quaternary public hospital in Australia. People with any cancer diagnosis attending the hospital were eligible. Data were analysed using inductive-deductive content analysis techniques. Twenty-two stakeholders (n = 10 cancer survivors of mixed-cancer types, n = 5 caregivers, and n = 7 social workers) participated. Key findings included: (i) genuine concern for FT of cancer survivors and caregivers shown through practical support by health care and social workers; (ii) need for clarity of role and services; (iii) importance of timely information flow; and (iv) proactive navigation as a priority. While cancer survivors and caregivers received financial assistance and support from the hospital, the lack of synchronised, shared understanding of roles and services in relation to finance between cancer survivors, caregivers, and health professionals undermined the effectiveness and consistency of these services. A proactive approach to anticipate cancer survivors’ and caregivers’ needs is recommended. Future research may develop and evaluate initiatives to manage cancer survivors and families FT experiences and outcomes. Full article

Immune checkpoint inhibitors (ICIs) for treatment of metastatic melanoma (MM) offer lasting overall survival (OS) benefit in a subset of patients. However, outcomes remain poor for non-responders. Clinical predictors of long-term survival remain elusive. We utilized the Alberta Immunotherapy Database to investigate the association of host and disease characteristics, and treatment factors with overall survival (OS) greater than 3 years. We identified patients treated between August 2013 and May 2020 with single-agent anti-PD1 or combination (anti-PD1 and anti-CTLA4) ICI regimens. A logistic regression model was used to assess for independent association between clinical factors captured and survival greater than 3 years. Statistically significant factors on univariable analysis were assessed using multivariable analysis. In total, 284 of 460 patients were identified to have short-term (<1 year) or long-term (>3 years) survival with 186 surviving <1 year and 98 surviving >3 years. The median age was 64 and 18.4% of patients were ECOG ≥ 2. On logistic regression, Breslow’s Depth ≤ 4 mm, normal serum LDH, normal serum albumin and M-stage 1a/b were associated with OS > 3 years on univariable and multivariable analysis. ECOG < 2, dNLR ≤ 3, normal hemoglobin were only associated with survival on the univariable analysis but not in the multivariable analysis. The objective response rate in long-term survivors was 83.7% compared to 7.5% in the short-term survivors. Our study identifies four easily accessible predictors of long-term survival in a large real-world MM cohort treated with ICI. Full article

Esophageal squamous cell carcinoma (ESCC) is a type of progressive and distant metastatic tumor. Targeting anti-angiogenic genes could effectively hinder ESCC development and metastasis, whereas ESCC locating on the upper or the lower esophagus showed different response to the same clinical treatment, suggesting ESCC location should be taken into account when exploring new therapeutic targets. In the current study, to find novel anti-angiogenic therapeutic targets, we identified endothelial cell subsets in upper and lower human ESCC using single-cell RNA sequencing (scRNA-seq), screened differentially expressed genes (DEGs), and performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The results showed that common DEGs shared in the upper and the lower endothelial cells mainly are involved in vessel development, angiogenesis, and cell motility of endothelial cells by regulating PI3K-AKT, Rap1, Ras, TGF-beta, and Apelin signaling pathways. The critical regulatory genes were identified as ITGB1, Col4A1, Col4A2, ITGA6, LAMA4, LAMB1, LAMC1, VWF, ITGA5, THBS1, PDGFB, PGF, RHOC, and CTNNB1. Cell metabolism-relevant genes, e.g., MGST3, PNP, UPP1, and HYAL2 might be the prospective therapeutic targets. Furthermore, we found that DEGs only in the upper endothelial cells, such as MAPK3, STAT3, RHOA, MAPK11, HIF1A, FGFR1, GNG5, GNB1, and ARHGEF12, mainly regulated cell adhesion, structure morphogenesis, and motility through Phospholipase D, Apelin, and VEGF signaling pathways. Moreover, DEGs only in the lower endothelial cells, for instance PLCG2, EFNA1, CALM1, and RALA, mainly regulated cell apoptosis and survival by targeting calcium ion transport through Rap1, Ras, cAMP, Phospholipase D, and Phosphatidylinositol signaling pathways. In addition, the upper endothelial cells showed significant functional diversity such as cytokine-responsive, migratory, and proliferative capacity, presenting a better angiogenic capacity and making it more sensitive to anti-angiogenic therapy compared with the lower endothelial cells. Our study has identified the potential targeted genes for anti-angiogenic therapy for both upper and lower ESCC, and further indicated that anti-angiogenic therapy might be more effective for upper ESCC, which still need to be further examined in the future. Full article

Background: Recently published clinical pathways for management of thyroid cancer outlined the criteria for transitioning low-risk patients to primary care within one to five years from diagnosis. However, discharge patterns among endocrinologists remain heterogeneous as there lacks a consensus regarding post-treatment care for thyroid cancer patients. Objective: This study described general characteristics and outcomes of thyroid cancer patients who were discharged from specialist care and transitioned to a primary care-based follow-up clinic. Methods: Thyroid cancer patients seen in the After Cancer Treatment Transition (ACTT) clinic at Women’s College Hospital (Toronto, Canada) were included in the study. Electronic medical records were reviewed between May and October 2021 to collect patient characteristics and outcomes. Descriptive statistics were calculated. Results: The study cohort included 148 thyroid cancer patients and 76% were female. All cases were papillary thyroid cancer and most diagnoses were classified as T₂ (42%), N₀ (55%), M₀ (91%), and stage 1 (83%). Nearly all patients (n = 147) had complete thyroidectomy. Levels of thyroglobulin and thyroglobulin antibodies (TgAb) were low overall, with only 5% of the study cohort deemed TgAb positive. Mean levels of thyroid stimulating hormone (TSH) measured at 2 time points (1.37 mIU/L, 1.42 mIU/L) were within normal range. About 91% of the study cohort had normal TSH levels and 82% met target TSH levels. There were 2 cases of recurrence; however, investigation determined that they were not initially appropriate candidates for transition to primary care. Nearly 99% (n = 146) of patients had excellent response to therapy, showed no evidence of disease recurrence, and have not required re-referral to specialist care. Conclusions: These findings may reassure specialists that low-risk, stable thyroid cancer patients can be safely transitioned to primary care for post-treatment follow-up. Full article

The main features of a giant cell tumor of bone (GCTB) are frequent recurrence and aggressive osteolysis, which leads to a poor prognosis in patients. Although the treatment methods for a GCTB, such as scraping and resection, effectively inhibit the disease, the tendency toward malignant transformation remains. Therefore, it is important to identify new treatment methods for a GCTB. In this study, we first found high Siglec-15 expression in GCTB tissues, which was significantly associated with Campanacci staging and tumor recurrence. In Spearman’s analysis, Siglec-15 expression was significantly correlated with Ki-67 levels in tumor tissues. In vitro, the mRNA and protein levels of Siglec-15 were high in GCTB stromal cells (Hs737. T), and Siglec-15 knockdown inhibited the biological characteristics of GCTB stromal cells. The RNA sequencing results enabled a prediction of the downstream genes by using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and MCODE analyses, and the findings showed that CXCL8 was significantly regulated by Siglec-15 and might be a promising downstream target gene of Siglec-15. Therefore, Siglec-15 may be a potential immunotherapy target for a GCTB. Full article

This study aimed to use a new special inventory for lung surgery patients to evaluate postoperative symptoms and functional status and to identify factors that may affect these after uniportal video-assisted thoracoscopic surgery (VATS). In this single-center longitudinal cohort observational study, we used a new scale, the perioperative symptom assessment for lung surgery (PSA-Lung), to evaluate the recovery from symptoms and the functional status of patients undergoing uniportal VATS. We divided patients into two groups, according to patients’ symptom scores, and compared the clinical characteristics between the two groups under each item. Then, we conducted a qualitative interview regarding coughing in postoperative week 4. Exactly 104 patients were enrolled in this study. The two highest-scoring patient-reported outcome (PRO) items were “shortness of breath” and “coughing” in the fourth week after surgery. Thirty-one patients reported that “coughing” severely influenced their lives in postoperative week 4. Using the PSA-Lung inventory, we found that “shortness of breath” was the worst symptom in postoperative week 4. Although “coughing” was not the most important symptom in the early postoperative period, it affected some patients’ lives in postoperative week 4. Therefore, further research is required to determine the optimal cut-off point for coughing. Full article

Angioimmunoblastic T-cell lymphoma is one of the peripheral T-cell lymphomas. Reactive plasma cells can occasionally be observed in AITL patients’ peripheral blood and bone marrow. Plasmacytic pleural effusion as the presentation of AITL has not been reported before. The mechanisms of plasmacytic pleural effusion are not fully understood. Here we present an 82-year-old male with exuberant plasma cells in his pleural effusion in addition to his peripheral blood and bone marrow aspiration. By presenting this case, we would like to expand the spectrum of disease presentations in AITL and discuss the significance of flow cytometry in the differential diagnosis of pleural effusion. To our knowledge, this is the first case report in the literature, which will be crucial to assist the hematopathologist in accurate diagnosis and treatment. Full article

Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC). Publicly available HTA recommendations and reports for oncology drugs issued by CADTH over a 2-year period, 2019–2020, were identified and compared with the corresponding HTA documents from NICE and the PBAC. Reporting of key model characteristics and attributes, survival analysis methods, methodological criticisms, and re-assessment of the economic results were characterized using descriptive statistics. Dichotomous differences in the methodological criticisms observed between the three agencies were assessed using Cochran’s Q tests and substantiated using pairwise McNemar tests. Chi-squared tests were used to assess the dichotomous differences in the reporting of methods and explore the potential relationships between categorical variables, where appropriate. HTAs published by CADTH, NICE, and the PBAC consistently reported a broad spectrum of descriptive information on the economic models submitted by manufacturers. While common economic evaluation attributes were well-reported across the three HTA agencies, significant differences in the reporting of survival analysis methods and methodological criticisms were observed. NICE consistently reported more comprehensive information, compared to either CADTH or PBAC. Despite these differences, broadly similar recommendation rates were observed between CADTH and NICE. The PBAC was found to be more restrictive. Based on our 2-year sample of oncology, the HTAs published by CADTH matched with the corresponding HTAs from NICE and PBAC; we observed important variations in the reporting of economic evidence, especially technical aspects, such as survival analysis, across the three agencies. In addition to guidelines for HTA submissions by manufacturers, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ. Full article