Comprehensive Review of Cranial Chordomas Using National Databases in the USA

AimsThe management of cranial chordomas is controversial. We provide a comprehensive review of the evolving patterns of care of cranial chordomas in the USA.Materials and methodsWe analysed the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2014 for clinical characteristics and long-term survival, and the National Surgical Quality Improvement Program (NSQIP) dataset between 2005 and 2016 for perioperative characteristics and surgical morbidity.ResultsIn total, 936 patients were identified from the NCDB, 405 patients from SEER and 64 patients from the NSQIP. Most patients were men (56.2, 54.8 and 57.8% in NCDB, SEER and NSQIP, respectively) and White (80.9 and 83.2% in NCDB and SEER, respectively). Surgery was the preferred treatment modality (87.3% in NCDB and 86.2% in SEER). Surgery was carried out alone (41.8% in NCDB and 40.7% in SEER) or in combination with radiation (42.1% in NCDB and 45.4% in SEER). Proton therapy was the most common type of radiation (32.2% in NCDB), particularly after 2011. The median operative time, median hospital length and postoperative morbidity were significantly higher in chordoma patients compared with patients who underwent other skull-base procedures. The 5-year survival rate was 79.8% in NCDB and 76.9% in SEER. There was a trend towards longer survival in patients receiving surgery and radiation, which has been increasingly used since 2004. Patients younger than 60 years had a decreased risk of mortality.ConclusionsOur analysis reflects patterns of care in the USA. The use of surgery and radiation is increasing, with a trend towards longer survival. Surgery is complicated with long operative time, hospital stay and a higher rate of complications.     

Importance of Multiparametric Evaluation of Immune-Related T-Cell Markers in Renal-Cell Carcinoma

Immunotherapeutic therapies such as immune checkpoint inhibitors have been used in patients with renal cell carcinoma (RCC). To overcome therapeutic resistance or identify predictive markers, a comprehensive understanding of the immunologic condition in the tumor microenvironment is important. We reviewed the latest scientific findings on the comprehensive immunologic condition within the tumor microenvironment in patients with RCC and its clinical significance. The immunologic condition evaluated by 3 different methods (flow cytometry, mass cytometry, and next-generation sequencing) in 4 different cohorts of patients with RCC could commonly divide the immunologic condition into 2 or 3 groups, all of which were significantly correlated with tumor aggressiveness and patient prognosis. In particular, patients with high T-cell infiltration and immunosuppressive cells including regulatory T cells had the worst prognosis in each cohort. This classification correlated with angiogenesis and metabolism and glycolysis, and it suggested that distinct biology exists in each immunologic classification. Moreover, around 20% to 30% of the RCC patients had intratumor immunologic diversity within each individual; this might help in understanding the presence of radiologic heterogeneity for immunotherapies. In conclusion, a comprehensive understanding of the immune condition is needed for the upcoming era of novel cancer immunotherapy using not only genetic but also phenotypic and functional classifications.     

FDA analyses of survival in older adults with metastatic non–small cell lung cancer in controlled trials of PD-1/PD-L1 blocking antibodies

Background

Among patients with newly diagnosed non–small cell lung cancer (NSCLC), approximately 70% occur in those above 65 years of age and more than half are metastatic or locally advanced NSCLC.

Impact on Health-Related Quality of Life of Induction Chemotherapy Compared With Concurrent Cisplatin and Radiation Therapy in Patients With Head and Neck Cancer

AimsOrgan preservation, an important goal in the treatment of head and neck squamous cell carcinoma (HNSCC), may include induction chemotherapy and cisplatin with radiation therapy (CRT). To our knowledge, no reports have directly compared the impact of induction chemotherapy with that of CRT on health-related quality of life (HRQOL).Materials and methodsIn a phase II trial, we assessed the HRQOL of patients treated with induction chemotherapy followed by CRT. Eligible patients had stage III–IV HNSCC. HRQOL questionnaires were administered at baseline, the end of induction (EOI), the end of CRT (EOCRT) and after CRT. Functional Assessment of Cancer Therapy (FACT version 4) assessed HRQOL. We carried out a comparison of changes in HRQOL from baseline to EOI and from EOI to EOCRT. This trial is registered with ClinicalTrials.gov (NCT01566435).ResultsThirty patients were enrolled in the study. Most HRQOL questionnaires were completed (88%). The mean total FACT scores did not differ from baseline to EOI (general: 83.8 versus 79.1, P = 0.08; head and neck: 109.7 versus 105.8, P = 0.33; Total Outcome Index: 69.7 versus 62.3, P = 0.03; respectively, using P ≤ 0.01 to adjust for multiple simultaneous tests of differences). However, total FACT scores significantly worsened from EOI to EOCRT (79.1 versus 62.3, P = 0.01; 105.8 versus 74.2, P < 0.01; 62.3 versus 34.2, P = 0.01; respectively). Within domains, the head and neck cancer subscale score did not differ from baseline to EOI (median 28.5 versus 27.0, P = 0.69), but significantly worsened from EOI to EOCRT (27.0 versus 9.5, P < 0.01). Swallowing, oral pain and voice quality improved from baseline to EOI, but worsened from EOI to EOCRT. Physical and functional scores worsened from baseline to EOI and from EOI to EOCRT. The emotional well-being score improved from baseline to EOI but worsened from EOI to EOCRT.ConclusionsOverall, HRQOL did not significantly change from baseline to EOI but dramatically worsened from EOI to EOCRT.     

An Overview of Uncommon Cutaneous Malignancies,Including Skin Appendageal (Adnexal) Tumours and Sarcomas

A standardised classification of malignant skin appendageal (adnexal) tumours and sarcomas is required for improved patient management and prognosis. This has been hindered by considerable morphological variation both within and between tumour types, the use of many synonyms for the same tumour types and variation in classification between pathologists.This update uses the improved classification in the 2018 WHO classification of skin tumours as the basis to discuss malignant skin appendageal tumours, sarcomas and cutaneous metastases that regularly present to skin cancer clinicians, multidisciplinary skin cancer teams and tumour boards, with current evidence for management, where appropriate.     

Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort

AimsTo report the outcomes of induction chemotherapy (ICT) followed by chemoradiotherapy (CTRT) for a large cohort of locoregionally advanced nasopharyngeal cancer (LA-NPC) from a non-endemic region.Materials and methodsBetween January 2008 and July 2015, 201 patients with histologically proven, non-metastatic NPC were treated with ICT followed by CTRT at our institute. All the patients received two to three cycles of a taxane-based ICT regimen. Radiotherapy was delivered using an intensity-modulated radiotherapy (IMRT) technique in all patients.ResultsAfter a median follow-up of 37 months (range: 7–110 months), the 3-year disease-free survival (DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival of the entire cohort was 72, 85, 83 and 87.4%, respectively. On multivariate analysis, histology was an independent predictor of DFS, LRFS and overall survival, with keratinising squamous cell carcinoma histologies predicting a worse outcome. The nodal stage was an independent predictor of DFS, DMFS and overall survival. Age, gender, ethnicity, tumour stage and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 19% of patients at last follow-up and grade 2 or worse xerostomia was seen in 24% of patients. Thirty-nine per cent of patients developed clinical hypothyroidism at last follow-up.ConclusionICT followed by concurrent CTRT in the IMRT era provides excellent locoregional control, distant control and overall survival rates in patients with LA-NPC. However, distant failure continues to be a problem and may require further systemic intensification.     

Who Can Avoid Systematic Biopsy Without Missing Clinically Significant Prostate Cancer in Men Who Undergo Magnetic Resonance Imaging-Targeted Biopsy?

BackgroundThe objective of the study was to identify a subset of men who can avoid systematic multisite biopsy (SyB) among those undergoing magnetic resonance imaging (MRI)-targeted transperineal 4-core biopsy (TgB) without missing clinically significant cancer (SC).Patients and MethodsFrom April 2013 to December 2017, 304 men with elevated prostate-specific antigen levels (< 20 ng/mL) or abnormal digital rectal examination and positive MRI findings underwent transrecta ultrasound and MRI-targeted transperineal 4-core with 14-core systematic biopsy. MRI findings were prospectively collected and evaluated using Prostate Imaging-Reporting and Data System version 2 (PI-RADS), and scores ≥3 were considered positive. SC was defined as Gleason score ≥3 + 4 or maximum cancer length ≥5 mm. We evaluated the diagnostic performance of TgB and SyB to detect SC and characterized men who could avoid SyB without missing SC.ResultsDetection rates of any cancer and SC for TgB/SyB/their combination were 59%/63%/68% and 51%/52%/61%, respectively. TgB alone missed 14% (29/207) of any cancer and 16% (29/184) of SC detected using TgB with SyB. In uni- and multivariable analyses, PI-RADS scores of 3 to 4 were independent predictors for missing SC using TgB alone. When restricted to 81 men with PI-RADS scores of 5 (27%), SC was missed using TgB alone only in 3 (4.6% vs. 22% for the remaining 223 men; P = .007).ConclusionSC was missed using TgB alone in a non-negligible proportion of men who underwent TgB and SyB. SyB might be safely avoided in men with PI-RADS score 5 lesions with reduced risks of missing SC.     

Phase 1 Study of Cabozantinib in Japanese Patients With Expansion Cohorts in Non–Small-Cell Lung Cancer

BackgroundCabozantinib inhibits tyrosine kinases including MET, AXL, VEGFR2, RET, KIT, and ROS1 and has demonstrated antitumor activity in multiple tumor types. The primary objective of this phase 1 study (NCT01553656) was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of cabozantinib in Japanese patients.Patients and MethodsPatients with advanced solid tumors were enrolled at 2 sites in Japan. After determining the MTD and RP2D, an expansion in non–small-cell lung cancer (NSCLC) consisting of 3 molecularly defined cohorts (EGFR mutation; KRAS mutation; ALK, RET, or ROS1 fusion) was initiated. The study was registered with ClinicalTrials.gov (NCT01553656).ResultsForty-three Japanese patients were enrolled (dose escalation, n = 23; NSCLC expansion, n = 20). The MTD of cabozantinib capsules was 60 mg daily, and the RP2D of cabozantinib tablets was 60 mg daily. Dose-limiting toxicities were hypertension, proteinuria, and venous embolism. Safety and pharmacokinetics in Japanese patients were consistent with those in non-Japanese patients. Common adverse events included palmar–plantar erythrodysesthesia, hypertension, and diarrhea. Reduction in tumor lesion size was observed in multiple tumor types in the dose-escalation cohorts, with partial responses observed in 4 of 9 patients with NSCLC (EGFR mutation, n = 1; ALK fusion, n = 2; and RET fusion, n = 1). In the NSCLC expansion, 4 patients with EGFR-mutant NSCLC had partial responses; the remaining 16 (EGFR mutation, n = 11; KRAS mutation, n = 2; ALK fusion, n = 1; and RET fusion, n = 2) had stable disease as best response.ConclusionCabozantinib had a manageable safety profile in Japanese patients with solid tumors. Responses were observed in diverse molecular subtypes of NSCLC.     

Electrochemotherapy and Ablative Therapies in Non-melanoma Skin Cancer

Although surgery and radiotherapy remain the most commonly used treatments for non-melanoma skin cancer, there are a variety of alternatives. Here we discuss the use of electrochemotherapy and ablative treatments and examine the evidence for their effectiveness against a number of non-melanoma skin cancers.     

Current Role of Radiotherapy in Non-melanoma Skin Cancer

Non-melanoma skin cancer (NMSC) represents the most frequently diagnosed malignancy worldwide, most being cutaneous basal cell and squamous cell carcinoma. The global incidence of NMSC continues to increase as the global population ages. Numerous treatment options are available for NMSC patients, with radiotherapy an efficacious and tissue-preserving non-surgical option. External beam radiotherapy and brachytherapy are modalities with specific indications and advantages in treating NMSC. Where excision is not an option (medically/technically inoperable) or considered less ideal (e.g. cosmetic or functional outcome), radiotherapy offers an excellent alternative. Inoperable elderly and/or co-morbid patients of poor performance status can benefit from short-course hypofractionated radiotherapy, with very acceptable toxicity. Adjuvant radiotherapy in patients with unfavourable pathology can decrease the risk of local and regional recurrence and associated morbidity and mortality. Radiotherapy has advantages and disadvantages and it is important for clinicians to understand these. Managing patients with NMSC is carried out by clinicians from multiple disciplines but it is imperative that they are all aware of the role of radiotherapy in their patients in various clinical settings. Here we aim to discuss the role and indications for recommending radiotherapy in patients with NMSC.     

A Prospective Study of Magnetic Resonance Imaging Assessment of Post-radiation Changes Following Stereotactic Body Radiation Therapy for Non-small Cell Lung Cancer

AimsFollow-up computed tomography scans after lung stereotactic body radiation therapy (SBRT) are difficult to interpret due to the presence of benign fibrosis, which can make the detection of local recurrence difficult. The objective of this study was to determine the feasibility of a novel thoracic magnetic resonance imaging (MRI) protocol incorporating diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging for the assessment of the treated lung parenchyma after SBRT.Materials and methodsOn a prospective trial, post-treatment MR images were acquired in 30 patients treated with SBRT (divided into three different cohorts according to the likelihood of local recurrence as per an expert panel). These images were assessed by an expert thoracic radiologist blind to clinical data, who indicated local recurrence in a dichotomous manner. Local recurrence was confirmed by biopsy or subsequent growth on follow-up computed tomography scans.ResultsThirty patients underwent MRI as part of this study; 27/30 patients were analysable for local recurrence. MRI was conducted at a median of 27.3 months (range 6.5–71 months) from SBRT. No side-effects resulted from either MRI or contrast administration. At a median follow-up time of 45 months after treatment, three local recurrence episodes have occurred. MRI assessment diagnosed seven patients as having a local recurrence, which was later confirmed in three and did not miss any of the true local recurrences. When comparing apparent diffusion coefficient (ADC) values according to local recurrence, the mean ADC value for the local recurrence-free group was 1770 × 10^?3 mm/s² (range 1038–3105 × 10^?3 mm/s²) versus 981 × 10^?3 mm/s² (range 926.6–1065 × 10^?3 mm/s²) for the local recurrence group (P = 0.0014).ConclusionsA novel 3.0 T MRI protocol incorporating DWI and DCE was feasible and confirmed the suspicion of local recurrence in patients with highly suspicious computed tomography scans. This imaging tool could potentially aid in selecting patients for salvage treatment after local SBRT failure. Future work should be pursued to validate these findings.     

Validation of the IMDC Prognostic Model in Patients With Metastatic Renal-Cell Carcinoma Treated With First-Line Axitinib: A Multicenter Retrospective Study

BackgroundThe objective of the study was to validate the characteristics of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model in patients treated with first-line axitinib in clinical practice.Patients and MethodsWe retrospectively evaluated 143 patients with metastatic renal-cell carcinoma who were treated with axitinib as the first-line therapy between October 2008 and February 2019. Overall survival (OS) was evaluated according to the IMDC prognostic model. We investigated the intragroup heterogeneity in the intermediate-risk group and divided these patients according to abnormal C-reactive protein (CRP) levels. An inverse probability of treatment-weighted (IPTW)-adjusted Cox regression analysis was performed to evaluate the effects of the CRP-risk model of OS in the patients in the IMDC intermediate-risk group.ResultsA significant difference in OS was observed in patients in the IMDC intermediate- and poor-risk group, although no significant difference was observed between the IMDC favorable- and intermediate-risk group. Significantly shorter prognosis was observed in patients in the IMDC intermediate-risk group who had 2 risk factors and CRP ≥0.3 mg/dL (inter-high group) than in those with 1 risk factor or 2 risk factors with CRP <0.3 mg/dL (inter-low group). IPTW-adjusted Cox regression analysis revealed significant differences in the OS between the inter-low and inter-high groups.ConclusionThe IMDC prognostic model was active in patients who received first-line axitinib treatment. The combination of CRP value with the number of positive risk factors in the IMDC model might predict prognosis in patients with IMDC intermediate-risk treated with first-line axitinib.     

Synchronous Bilateral RCC Is Associated With Poor Recurrence-Free Survival Compared With Unilateral RCC: A Single-Center Study With Propensity Score Matching Analysis

BackgroundUnderstanding the tumorigenesis of bilateral cancers occurring in paired organs is essential for treatment planning and follow-up strategies. To the best of our knowledge, only a few studies compared the survival outcomes in patients with unilateral and bilateral renal cell carcinoma (RCC). We aimed to evaluate the survival outcomes of these patients after surgery and perform a further comparison of synchronous and metachronous bilateral RCCs.Materials and MethodsWe analyzed clinical data from a total of 2169 patients (98.0%) diagnosed with unilateral RCC and 44 patients (2.0%) diagnosed with bilateral RCC including 22 (50.0%) with synchronous (diagnosed concomitantly or within 3 months of the former tumor) and 22 (50.0%) with metachronous RCC at our institution. Comparative analysis of unilateral and bilateral RCC groups was conducted using propensity score matching analysis. Subgroup analysis of bilateral RCC including synchronous and metachronous RCCs was also performed.ResultsKaplan–Meier survival analysis showed a significantly decreased 5-year recurrence-free survival (RFS; 82.6% vs. 94.3%; log rank test, P = .045) in the bilateral RCC group compared with the unilateral group. In subgroup analysis, the metachronous RCC group showed significantly smaller mean pathologic tumor size (P = .011), and more favorable pathologic T stage (P = .036) compared with the synchronous RCC group. Kaplan–Meier survival analysis showed significantly decreased 5-year RFS in synchronous RCC compared with metachronous RCC (74.7% vs. 92.9%; log rank test, P = .028).ConclusionThe bilateral RCC group showed significantly decreased 5-year RFS compared with the unilateral RCC group. Importantly, the synchronous RCC group manifested more adverse features than the metachronous group.     

Global Collaborations for Cervical Cancer: Can the East–West Alliance Facilitate Treatment for all?

Despite the advances in the primary prevention of cervical cancer, there is an absolute increase in the incidence of cervical cancer as a result of an increase in world population. A vast majority of patients in low and low–middle income countries continue to present at a locally advanced stage, necessitating treatment with chemoradiation and brachytherapy. There is a dearth of equipment and trained professionals for the treatment of cervical cancer, especially in low and low–middle income countries. There is an urgent need to improve treatment availability and develop better treatments. Worldwide trends, however, reveal a low number of therapeutic and innovative research trials in cervical cancer. The present article elucidates the existing challenges and provides solutions to improve outcomes. The proposed strategies hinge on strengthening collaborations for global advocacy.     

Neurotoxicity Among Survivors of Testicular Cancer: A Population-based Study

AimsNeurotoxicity may affect the quality of life of survivors of testicular cancer. Understanding the burden of neurotoxicity is important to guide survivorship care. A population-based study was undertaken to describe the proportion of patients in the ‘real world’ with neurotoxicity.Materials and methodsA population-based, retrospective, cohort study of patients with advanced testicular cancer treated in the province of Ontario. The Ontario Cancer Registry was linked to electronic treatment records to identify all incident cases of testicular cancer during 2000–2010. Administrative databases were used to describe health system visits for symptoms potentially related to neurotoxicity. Health system visit rates were explored by number of chemotherapy cycles among patients treated during 2005–2010 for whom complete chemotherapy details were available.ResultsDuring 2000–2010, 2650 patients underwent an orchiectomy for testicular cancer; 920 (33%) also received chemotherapy. The proportion of patients with health system visits for neurotoxicity in the 2 years before surgery compared with the 2 years after surgery remained stable among patients treated with orchiectomy alone (18% [303/1730] versus 18% [316/1730], P = 0.523); however, there was a substantial increase among patients treated with chemotherapy (16% [151/920] versus 25% [231/920], P < 0.001). Among patients treated with chemotherapy in 2005–2010 for whom complete details were available regarding number of treatment cycles there was a dose–response effect. The increase in health system visits for neurotoxicity from 2 years before compared with 2 years after orchiectomy was greater among patients treated with four cycles of chemotherapy (17% [21/121] versus 37% [45/121]) and three cycles of chemotherapy (17% [45/258] versus 28% [72/258]) compared with those treated with one to two cycles of chemotherapy (<13% [<6/45] versus 20% [9/45], P = 0.013).ConclusionsThis population-based study suggests that symptoms of neurotoxicity are common among survivors of testicular cancer and that this seems to be driven by increasing exposure to chemotherapy. Clinicians should carefully evaluate patients for neurotoxicity during the survivorship phase of treatment.     

Comparison of Methods for Measuring Radiotherapy Utilisation

AimsEvidence-based estimates of appropriate rates of radiotherapy utilisation are usually stated as the proportion of cancer patients who should receive radiotherapy at least once in their lifetime. However, the prolonged follow-up required to measure the lifetime radiotherapy rate limits its value in monitoring access to radiotherapy in routine practice. The objectives of this study were to evaluate shorter-term methods for measuring radiotherapy utilisation and to determine how well they predict the lifetime radiotherapy rate.Materials and methodsThe Ontario Cancer Registry provided records of all cases of cancer diagnosed in Ontario between 1984 and 2015. Records of all radiotherapy delivered by Ontario cancer centres were linked to individual cases in the Ontario Cancer Registry. Patients were followed forward for 20 years to determine the relationship between short-term and long-term rates of use of radiotherapy. Radiotherapy utilisation was also estimated by comparing total radiotherapy workload with cancer incidence; these measures were compared with observed long-term radiotherapy rates.ResultsThe rate of use of radiotherapy within 1 year of diagnosis (RT_1y) was strongly predictive of the rate of use of radiotherapy after 20 years (RT_20y); for each annual cohort of cases between 1984 and 1995, RT_20y was approximately equal to 1.3 × RT_1y. The number of cases treated for the first time with radiotherapy in a specified period, divided by the number of new cases diagnosed in the same period, was about equal to the proportion of cases treated with radiotherapy within 20 years of diagnosis (RT_20y).ConclusionsThe lifetime rate of use of radiotherapy may be predicted quite accurately from the rate observed within 1 year of diagnosis, or from the ratio of new cases treated to cancer incidence in a specified period. Either of these measures may therefore be used to audit radiotherapy utilisation against the existing evidence-based targets.