Curr. Oncol., Volume 29, Issue 5 (May 2022) – 69 articles

Human papillomavirus (HPV) vaccination prevents cervical, head and neck, and anogenital cancers. However, global HPV vaccine coverage falls short of global targets and has seen unexpected and dramatic declines in some countries. This paper synthesizes the impact of HPV on the global burden of cancer and the potential benefit of HPV vaccination. Approximately 5% of the world’s cancers are specifically attributed to HPV. While the greatest global burden of HPV is cervical cancers in low- and middle-income countries, HPV-associated head and neck cancers are increasing in high-income countries and have surpassed cervical cancer as the primary HPV-associated cancer in some countries. Therefore, it is also critical to improve gender-neutral HPV vaccination. Understanding the modifiable drivers of vaccine acceptance and uptake is important for increasing HPV vaccination. The Behavioural and Social Drivers of Vaccination framework is broadly applied to identify key factors associated with HPV vaccination including domains concerning practical issues, motivation, social processes, and thinking and feeling. Among the behavioural strategies available to reduce the incidence and mortality of cancer, increasing HPV vaccination stands out as having unrealized potential to prevent disease, financial cost, and psychological distress. An understanding of the shifting burden of HPV and the factors associated with vaccination can be leveraged to regularly measure these factors, develop interventions to promote vaccine uptake, and improve global HPV vaccine coverage. Future research in diverse contexts is necessary to investigate the barriers and facilitators of global HPV vaccination. Full article

Although laser vaporization is a popular minimally invasive treatment for cervical intraepithelial neoplasia (CIN), factors influencing CIN recurrence are understudied. Moreover, the effect of surgeon volume on patients’ prognosis after laser vaporization for CIN is unknown. This single-center retrospective study evaluated the predictive value of surgeon volume and patient characteristics for laser vaporization outcomes in women with pathologically confirmed CIN2. Histologically confirmed CIN2 or higher grade after laser vaporization was defined as persistent or recurrent. Various patient characteristics were compared between women with and those without recurrence to examine the predictive factors for laser vaporization. There were 270 patients with a median age of 36 (18–60) years. The median follow-up period was 25 (6–75.5) months and the median period between treatment and persistence or recurrence was 17 (1.5–69) months. The median annual number of procedures for all seven surgeons was 7.8. There were 38 patients (14.1%) with persistent or recurrent lesions—24 had CIN2, 13 had CIN3, and one had adenocarcinoma in situ. Patient age, body mass index, surgeon volume, and history of prior CIN treatment or invasive cervical cancer were not significantly correlated with lesion persistence or recurrence. In conclusion, laser vaporization has comparable success rates and is a feasible treatment for both low- and high-volume surgeons. Full article

Immunoproliferative small intestinal disease (IPSID) is an uncommon disease with a higher prevalence in the developing world. IPSID diagnosis relies mainly on a tissue biopsy and a high index of suspicion. Treatment options are variable; however, they mainly include anthracycline-based chemotherapy with or without antibiotics in advanced stages. Because of the paucity of IPSID, our perception of the disease remains narrow, and investigating the optimal lines of therapy and prevention without a complete comprehension of the disease is challenging. In our review, we explore the expansion of knowledge about IPSID, which has been developing over the years, to help increase the detection of IPISD cases and further research the most appropriate lines of therapy and prevention. Full article

Introduction: Assessment of actionable gene mutations and oncogene fusions have made a paradigm shift in treatment strategies of non-small cell lung cancer (NSCLC). HRAS mutations involved around 0.2–0.8% of NSCLC patients, mostly on codon 61. For these patients, few data are available regarding clinical characteristics and response to therapies. Methods: Next-Generation Sequencing (NGS) done routinely at Nantes University Hospital was used to identify HRAS molecular alterations in NSCLC patients. We identified and described four HRAS p.GlnQ61Leu mutated patients. Literature of previously HRAS-mutant NSCLC cases was reviewed, and available data in solid tumour with the most advanced H-Ras specific inhibitor, tipifarnib, were presented. Results: Of 1614 patients diagnosed with advanced NSCLC from January 2018 to December 2020, four (0.25%) had HRAS p.Gln61Leu mutation. Three of them died during the first-line systemic therapy. Furthermore, three additional cases were identified in literature. All cases were current or former smokers, most of them had pleural or pericardial effusion at diagnosis. Conclusions: The clinical course of patients with HRAS-mutant NSCLC remains unclear. Furthers cases should be identified in order to clarify prognosis and response to therapies. Tipifarnib, a farnesyl transferase inhibitor, is a promising candidate to target HRAS-mutant tumours and should be explored in NSCLC patients. Full article

There is a significant body of evidence that delivering tobacco dependency treatment within acute care hospitals can deliver high rates of tobacco abstinence and substantial benefits for both patients and the healthcare system. This evidence has driven a renewed investment in the UK healthcare service to ensure all patients admitted to hospital are provided with evidence-based interventions during admission and after discharge. An early-implementer of this new wave of hospital-based tobacco dependency treatment services is “the CURE project” in Greater Manchester, a region in the North West of England. The CURE project strives to change the culture of a hospital system, to medicalise tobacco dependency and empower front-line hospital staff to deliver an admission bundle of care, including identification of patients that smoke, provision of very brief advice (VBA), protocolised prescription of pharmacotherapy, and opt-out referral to the specialist CURE practitioners. This specialist team provides expert treatment and behaviour change support during the hospital admission and can agree a support package after discharge, with either hospital-led or community-led follow-up. The programme has shown exceptional clinical effectiveness, with 22% of all smokers admitted to hospital abstinent from tobacco at 12 weeks, and exceptional cost-effectiveness with a public value return on investment ratio of GBP 30.49 per GBP 1 invested and a cost per QALY of GBP 487. There have been many challenges in implementing this service, underpinned by the system-wide culture change and ensuring the good communication and engagement of all stakeholders across the complex networks of the tobacco control and healthcare system. The delivery of hospital-based tobacco dependency services across all NHS acute care hospitals represents a substantial step forward in the fight against the tobacco epidemic. Full article

Minimally invasive surgery may not be an appropriate surgical approach in intermediate- and high-risk endometrial carcinoma, even though adjuvant therapy is given. The objective of this study was to evaluate the results of open surgery including lymphadenectomy without adjuvant therapy in patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma. Two hundred fifty-six patients with uterine-confined endometrioid endometrial carcinoma were treated with open surgery, including pelvic with or without para-aortic lymphadenectomy. Of the 81 patients with uterine-confined intermediate- or high-risk disease, 77 were treated with systematic lymphadenectomy without adjuvant therapy. Seven patients developed recurrence, comprising 5.5% (3/55) and 18.2% (4/22) of the intermediate- and high-risk patients, respectively. The time to recurrence was 1–66 months. The sites of recurrence were the vaginal apex (n = 2), lung (n = 2), vaginal sidewall (n = 1), pelvic lymph nodes (n = 1), and para-aortic to supraclavicular nodes (n = 1). Of these, five patients were alive without disease after salvage treatment, but two understaged high-risk patients died of disease. The five-year disease-specific survival rates of intermediate- and high-risk patients were 100% and 90%, respectively. The present study indicated that patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma had excellent survival when treated with open surgery, including lymphadenectomy alone. The safety of omitting adjuvant therapy should be evaluated in prospective randomized trials comparing open surgery with minimally invasive surgery. Full article

Neoadjuvant short course radiotherapy (SCRT) followed by consolidation chemotherapy (CCT) is an alternative treatment for locally advanced rectal cancer (LARC). We performed this systematic review and meta-analysis to explore the tumor response and oncological outcomes of this new approach compared to conventional chemoradiotherapy (CRT). An online search of the PubMed, Embase, and Cochrane Library databases was performed. This review included 7507 patients from 14 different cohorts. The pCR rate was higher with SCRT + CCT than that with CRT (RR: 1.60; 95% CI: 1.35–1.91; p < 0.01). SCRT + CCT provided a higher ypN0 response (RR: 1.06; 95% CI: 1.01–1.12; p = 0.02). There were no differences in R0 resection and positive CRM rates; however, more sphincter-preservation surgeries were performed in the SCRT + CCT arm (RR: 1.06; 95% CI: 1.01–1.11; p = 0.02). There was no difference in the OS and DFS between the SCRT + CCT and the CRT arms (OS: HR: 0.85, p = 0.07; DFS: HR: 0.88, p = 0.08). The compliance and toxicity were comparable between the SCRT and CRT groups. In the subgroup analysis, patients who underwent four or more cycles of CCT had better pCR and DFS events. Therefore, SCRT followed by consolidation chemotherapy might be an effective alternative treatment for LARC. Full article

Despite the known importance and necessity of the standardized collection and use of patient-reported outcomes (PROs), there remain challenges to successful clinical implementation. Facilitated through a quality improvement initiative spearheaded by the Canadian Partnership for Quality Radiotherapy (CPQR), and now guided by the Canadian Association of Radiation Oncology (CARO)’s Quality and Standards Committee, patient representatives and early-adopter radiation treatment programs continue to champion the expansion of PROs initiatives across the country. The current review discusses the evolution of a pan-Canadian approach to PROs use, striving to fill in gaps between clinical practice and guideline recommendations through multi-centre and multidisciplinary collaboration. Full article

The prevalence of oropharyngeal squamous cell carcinoma has been increasing in North America due to human papillomavirus-associated disease. It is molecularly distinct and differs from other head and neck cancers due to the young population and high survival rate. The treatment regimens currently in place cause significant long-term toxicities. Studies have transitioned from mortality-based outcomes to patient-reported outcomes assessing quality of life. There are many completed and ongoing trials investigating alternative therapy regimens or de-escalation strategies to minimize the negative secondary effects while maintaining overall survival and disease-free survival. The goal of this review is to discuss the most recent advancements within the field while summarizing and reviewing the available evidence. Full article

Ovarian seromucinous tumors (SMBTs) are relatively rare, and their carcinogenesis is largely unknown. In this study, the molecular features of SMBTs in Japan are assessed. DNA was extracted from microdissected paraffin-embedded sections from 23 SMBT cases. Genetic mutations (KRAS, BRAF, PIK3CA, and ERBB2) were evaluated using Sanger sequencing. Immunohistochemistry for p53, ARID1A, and PTEN was also performed as a surrogate for the loss of functional mutations in these tumor suppressor genes. The prevalence of KRAS, BRAF, PIK3CA, and ERBB2 mutations was 4.3% (1/23), 8.6% (2/23), 8.6% (2/23), and 17.3% (4/23), respectively. Overexpression or loss of p53 expression occurred in 26% (6/23), loss of ARID1A expression in 4.3% (1/23), and none of the cases showed expression of PTEN loss. These findings suggest that KRAS/BRAF/PIK3CA and PTEN mutations are rare carcinogenic events in SMBTs. The high frequency of positive p53 staining and a low frequency of loss of ARID1A staining suggests that SMBT carcinogenesis may be related to the alteration of p53 rather than that of ARID1A. ERBB2 oncogenic mutations may play an important role in the tumorigenesis of Japanese SMBTs. Full article

Chimeric antigen receptor T (CAR T) cell therapy achieved remarkable success in B-cell leukemia and lymphoma which led to its incorporation in treatment protocols for these diseases. CAR T cell therapy for chronic lymphocytic leukemia (CLL) patients showed less success compared to other malignant tumors. In this review, we discuss the published results regarding CAR T cell therapy of CLL, possible mechanisms of failures and expected developments. Full article

Background: To determine the risk of mortality and factors associated with survival amongst patients diagnosed with primary hepatic angiosarcoma (PHA). Methods: All patients diagnosed with hepatocellular carcinoma (HCC) or PHA from 2004 to 2014 were identified from the National Cancer Database (NCDB). Further analysis was performed within the cohort of patients with PHA to assess the impact of surgery, chemotherapy, radiation, and facility type on overall survival (OS). A multivariable analysis using the Cox proportional methods and a survival analysis using the Kaplan–Meier method were used. Results: A total of 117,633 patients with HCC were identified, out of whom 346 patients had PHA. Patients with PHA had a mean age of 62.9 years (SD 13.7), the majority were men (64.7%), white (85.8%), and had a Charlson comorbidity index (CCI) of zero (66.2%). A third of the patients with PHA (35.7%) received chemotherapy, and 14.6% underwent a surgical resection. The median survival was 1.9 months (1.8–2.4 months) compared to patients with HCC (10.4 months, 10.2–10.5) (aHR-2.41, 95% CI: 2.10–2.77, p < 0.0001). Surgical resection was associated with a higher median survival (7.7 versus 1.8 months, aHR-0.23, 95% CI: 0.15–0.37, p < 0.0001). A receipt of chemotherapy was associated with a higher median survival than no chemotherapy (5.1 versus 1.2 months, aHR-0.44, 95% CI: 0.32–0.60, p < 0.0001), although the survival benefit did not persist long term. Conclusion: PHA is associated with poor outcomes. A surgical resection and chemotherapy are associated with improved survival outcomes; however, the long-term benefits of chemotherapy are limited. Full article

The purpose of breast cancer screening is to find cancers early to reduce mortality and to allow successful treatment with less aggressive therapy. Mammography is the gold standard for breast cancer screening. Its efficacy in reducing mortality from breast cancer was proven in randomized controlled trials (RCTs) conducted from the early 1960s to the mid 1990s. Panels that recommend breast cancer screening guidelines have traditionally relied on the old RCTs, which did not include considerations of breast density, race/ethnicity, current hormone therapy, and other risk factors. Women do not all benefit equally from mammography. Mortality reduction is significantly lower in women with dense breasts because normal dense tissue can mask cancers on mammograms. Moreover, women with dense breasts are known to be at increased risk. To provide equity, breast cancer screening guidelines should be created with the goal of maximizing mortality reduction and allowing less aggressive therapy, which may include decreasing the interval between screening mammograms and recommending consideration of supplemental screening for women with dense breasts. This review will address the issue of dense breasts and the impact on the stage of breast cancer at the time of diagnosis, and discuss options for supplemental screening. Full article

Background: The management of cholangiocarcinoma is continually reviewed on a current evidence basis to develop practice guidelines and consensus statements. However, the standardized treatment guidelines are still unclear for cholangiocarcinoma patients who are listed for liver transplantation. We aimed to validate and evaluate the potential efficacy of chemotherapy combination of Gemcitabine and Cisplatin as a neo-adjuvant treatment for cholangiocarcinoma patients before liver transplantation. Methods: In this prospective case series, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with a combination of neoadjuvant gemcitabine and cisplatin with no radiation. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center according to an open-labeled, and center-approved clinical management protocol. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. Results: Between 1 March 2016, and 15 March 2022, 10 patients (8 males and 2 females) with a median age of 62.71(interquartile range: 60.02–71.87) had a confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma and underwent liver transplantation. Median days of neoadjuvant therapy for a given combination of gemcitabine and cisplatin were 181 (IRQ: 120–250). Nine patients (90%) were reported with no recurrence or metastasis, and only 1 patient had confirmed metastasis (10%); days for metastasis after transplantation were 612 for this patient. All patients received a combination of gemcitabine and cisplatin as neo-adjuvant while awaiting liver transplantation. The median days of follow-up were 851 (813–967). Overall survival was 100% (95% CI 100–100%) at both years one and two; 75% (95% CI 13–96%) at years three to five. One patient died at eight hundred and eighty-five days. No adverse events were reported after liver transplantation including the patient who was confirmed with recurrence. Conclusions: Our finding demonstrated that neo-adjuvant gemcitabine and cisplatin with no radiation prior to liver transplantation resulted in excellent outcomes for patients with cholangiocarcinoma. Full article

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. It originates from neoplasms of the appendix and leads to the formation of peritoneal implants and the accumulation of mucinous ascites. PMP represents a spectrum of low to high-grade disease. Despite aggressive management, many PMP patients recur, leading to debilitating symptoms and few treatment options. Therefore, scientists have continued to look for ways to improve treatment and further understand disease pathogenesis. Microorganisms were previously hypothesized to play a role in PMP progression and development. Hence, antibacterial treatment was suggested by some authors, but the data were limited. In this paper, we review the current data on the role of bacteria in PMP, discuss the significance, and suggest possible solutions to the inherent challenges in these studies. Given the limitations of the discussed studies, we remain skeptical about introducing novel antibacterial treatment into clinical practice at this time; however, the available data are valuable and indicate that more research into the molecular mechanisms of PMP is needed. Full article

Background: Up to 20% of women diagnosed with tubo-ovarian carcinoma carry a germline pathogenic variant in a cancer-predisposing gene (e.g., BRCA1/BRCA2). Identifying these variants can help to inform eligibility for therapies, guide surveillance and prevention of new primary cancers, and assess risk to family members. The Gynecologic Oncology-Initiated Genetic Testing Model (GOIGT) was initiated at the McGill University Health Centre (MUHC) to streamline universal germline genetic testing for this population, while addressing the limited resources in the public healthcare system. This study aimed to evaluate the patient experience of participating in this model. Methods: Study participants were patients diagnosed with high-grade non-mucinous epithelial tubo-ovarian cancer who underwent genetic testing through the GOIGT model between 1 January 2017 and 31 December 2020. Eligible participants completed the retrospective questionnaires at least one month after result disclosure. Results: A total of 126 patients were tested through the GOIGT model during the study period, of which 56 were invited to participate. Thirty-four participants returned the study questionnaire. Overall, participants did not report decision regret following the genetic testing and were satisfied with the GOIGT model. Participants reported low levels of uncertainty and distress related to the implications of their test results for themselves and their family members. Conclusions: The results of this study support the continued implementation of mainstreamed genetic testing models for women with high-grade non-mucinous tubo-ovarian cancer. Further studies are required to compare experiences for patients with different genetic test results. Full article

The inclusion of productivity costs can affect the outcome of cost-effectiveness analyses. We estimated the value of cancer premature mortality productivity costs for Europe in 2020 using the Human Capital Approach (HCA) and compared these to the Friction Cost Approach (FCA). Cancer mortality data were obtained from GLOBOCAN 2020 by sex and five-year age groups. Twenty-three cancer sites for 31 European countries were included. The HCA and the FCA were valued using average annual gross wages by sex and age group and applied to Years of Potential Productive Life Lost. 2020 friction periods were calculated and all costs were in 2020 euros. Estimated cancer premature mortality costs for Europe in 2020 were EUR 54.0 billion (HCA) and EUR 1.57 billion (FCA). The HCA/FCA cost ratio for Europe was 34.4, but considerable variation arose across countries (highest in Ireland: 64.5 v lowest in Czech Republic: 11.1). Both the HCA and the FCA ranked lung, breast and colorectal as the top three most costly cancers in Europe, but cost per death altered rankings substantially. Significant cost differences were observed following sensitivity analysis. Our study provides a unique perspective of the difference between HCA and FCA estimates of productivity costs by cancer site and country in Europe. Full article

Behind the science of breast cancer in Canada, as well as globally, are the stories of thousands of women, their families, and their communities. These include stories from those who have died or those suffering from the realities of stage III and stage IV breast cancer due to late detection, misinformation, and dismissal. The reality for these women is that, whilst grateful for the latest developments in cancer research, much of this knowledge is not reflected in policy and practice. Canadian guidelines do not reflect the recommended screening by experts within the field and inequities in screening practices and practitioner knowledge exist in different areas within Canada. Told through the stories of women with lived experiences of late-stage breast cancer and supported by scientific evidence, this paper explores the impact of outdated breast cancer screening practices on the lives of women. Recent patient advocacy is driving changes, such as notifying women of their breast density in a few jurisdictions in Canada, but we call for the whole medical community to take responsibility and ensure breast screening is optimised to save more lives. Full article

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of cancer-related mortality worldwide. It is responsible for 80–85% of lung cancer cases. NSCLC can be divided into several groups, led by adenocarcinoma (ADC)–40–50% and squamous cell carcinoma (SCC)–20–30%. The development of new molecular therapies targeting particular abnormalities such as mutations in the EGFR (Epidermal Growth Factor Receptor) gene or ROS1 or ALK genes rearrangements resolved in novel strategies in advanced NSCLC management. EGFR mutation occurs mostly in patients with ADC and those patients are mostly females with no or light smoking history. The hereby presented patient fitted the ADC characteristics, while they were diagnosed with SCC. The unusual diagnosis implied further genetic testing, which established the occurrence of L858R substitution in exon 21 in the EGFR gene. A 63-year-old female was admitted to the unit due to a dry cough, pain in the right chest area and dyspnoea. When diagnosed, the patient had a peripheral mass in the right lung superior lobe (55 × 40 mm), satellite nodules in the apex of the same lung and packets of disintegrating lymph nodes. Positron Emission Tomography (PET-CT) confirmed a diffuse neoplastic process qualified as stage IV on the TNM scale. Due to EGFR gene mutation, the woman was administered osimertinib, however, the treatment did not succeed, and other therapeutic solutions were undertaken. The patient died 10 months after diagnosis. Patients with advanced ADC harboring EGFR mutation can receive osimertinib, a third-generation tyrosine kinase inhibitor (TKI), however, the use of TKIs in SCC remains controversial. In some published cases, osimertinib treatment led to success, in others, the therapy did not result in the expected final effect. Small sample groups and diverse molecular backgrounds indicate the need for further research in this field. Thus, the treatment decision-making process in those patients overall remains extremely demanding and ambiguous. Full article

Background: The purpose of this study was to evaluate the implant survival, functional score and complications of intercalary endoprostheses implanted for metastatic involvement of the femoral and humeral diaphysis. Methods: The selected group covered patients with bone metastasis who were surgically treated with an intercalary endoprosthesis between 2012 and 2021. The functional outcome was evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system, and complications were evaluated by using the failure classification for prosthetics designed by Henderson. Results: The mean follow-up was 29.8 months. In our group of 25 patients with 27 intercalary endoprostheses (18 femurs, 9 humeri), there were 7 implant-related complications (25.9%), which were more common on the humerus (4 cases, 44.4%) than on the femur (3 cases, 16.7%). Only type II failure—aseptic loosening (5 cases, 18.5%)—and type III failure—structural failure (2 cases, 7.4%)—occurred. There was a significantly higher risk of aseptic loosening of the endoprosthesis in the humerus compared with that in the femur (odds ratio 13.79, 95% confidence interval 1.22–151.05, p = 0.0297). The overall cumulative implant survival was 92% 1 year after surgery and 72% 5 years after surgery. The average MSTS score was 82%. The MSTS score was significantly lower (p = 0.008) in the humerus (75.9%) than in the femur (84.8%). Conclusions: The resection of bone metastases and replacement with intercalary endoprosthesis has excellent immediate functional results with an acceptable level of complications in prognostically favourable patients. Full article

Urothelial carcinoma is a complex cancer with genomic immunomic drivers that have prognostic and predictive treatment implications. Identifying potential targetable alterations via next-generation sequencing and RNA sequencing may allow for elucidation of such targets and exploitation with targeted therapeutics. The role of immunotherapy in treating urothelial carcinoma has shown benefit, but it is unclear in which patients immunotherapeutics have the highest yield. Continuing efforts into better identifying which patients may benefit most from targeted therapies, immunotherapies, and combination therapies may ultimately lead to improved outcomes for patients with this disease. Full article

Selpercatinib, a RET kinase inhibitor, is an effective treatment for patients with medullary thyroid cancer with RET mutations. In this paper, we present the case of a 62-year-old man with ectopic Cushing’s syndrome due to medullary thyroid cancer who received treatment with selpercatinib. Six months later, all the cushingoid features had resolved, and s-calcitonin had decreased from 580 pmol/L to 3.5 pmol/L (normal < 3). After further 6 months, s-calcitonin had normalized (1.5 pmol/L), and radiological evaluation showed a profound tumour volume reduction. We are aware of two other cases where treatment with selpercatinib has also been successful. Thus, selpercatinib may be a promising treatment alternative in patients with ectopic Cushing’s syndrome due to medullary thyroid cancer, especially when other treatment options are ineffective or not tolerated. Full article

Heterogeneous masses developing in the pleural cavity are most often malignant and can pose diagnostic challenges. Fibrous tumors of the pleura, liposarcoma, thymoma or lipoma most frequently affect this anatomic area. Surgical exploration and resection are often mandatory to make the definitive diagnosis. We report the case of a 54-year-old women who presented with an epigastric and right sub costal pain. A complete preoperative workup revealed a large tissular and fatty mass in the right costo-diaphragmatic angle suggestive of liposarcoma. Surgical resection resulted in the surprising diagnosis of hamartochondroma. Full article

Glioblastomas with multiple foci at presentation (mGBMs) account for 2–35% of all GBMs. mGBMs have limited existing data and no standardized treatment. This study aims to determine their incidence, demographic and clinical features, outcome, and prognostic factors in terms of overall survival. We performed a monocentric retrospective study, reviewing patients treated at the Istituto Oncologico Veneto. Inclusion criteria were: new diagnosis of GBM and presence of multiple lesions on pre-treatment MRI. ECOG PS was used to evaluate clinical condition, RANO criteria for radiological assessment, and CTCAE v5.0 for treatment-related adverse events. The incidence of newly diagnosed mGBM was 7.2% and the study population consisted of 98 patients. Median age was 63 years, M:F ratio of 1.8:1, and a surgical approach was undertaken in 73 patients (mostly partial resection). MGMT was methylated in 47.5%, and 82 patients received active oncological treatment (65.9% radiotherapy plus temozolomide (RT + TMZ)). The disease control rate with RT + TMZ was 63%. Median OS of the entire study population was 10.2 months (95% CI 6.6–13.8), and median PFS was 4.2 months (95% CI 3.2–5.2). The ECOG PS, the extent of resection, and the RT + TMZ were significant prognostic factors in the univariate analysis for OS, but only the RT + TMZ was a significant independent OS predictor in the multivariate analysis (HR = 3.1, 95% IC 1.3–7.7, p = 0.014). The incidence of mGBM is not rare. RT + TMZ is confirmed to be an independent prognostic factor for survival and a safe and effective treatment. When feasible, RT + TMZ should be considered as a possible first-line treatment. The role of the extent of resection is still unclear. Full article

Background: Megaprosthetic reconstruction is sometimes indicated in advanced metastatic bone disease (MBD) of the appendicular skeleton with large degrees of bone loss or need for oncological segmental resection. Outcome after megaprosthetic reconstruction was studied in the setting of primary bone sarcoma with high levels of complications, but it is not known if this applies to MBD. Method: We performed a comparative analysis of complications and revision surgery for MBD and bone sarcoma surgery in an institutional cohort from 2005–2019. Presented are the descriptive data of the cohort, with Kaplan–Meier (K–M) rates of revision at 1, 2 and 5 years together with a competing risk analysis by indication type. Results: Rates of revision surgery are significantly lower for MBD (8% at 1 year, 12% at 2 years), in the intermediate term, compared to that of sarcoma (18% at 1 year, 24% at 2 years) (p = 0.04). At 5 years this is not significant by K–M analysis (25% for MBD, and 33% for sarcoma), but remains significant in a competing risk model (8% for MBD, and 20% for sarcoma) (p = 0.03), accounting for death as a competing event. Conclusion: Rates of revision surgery after megaprosthetic reconstruction of MBD are significantly lower than that for primary bone sarcoma in this cohort. Full article

Primary mediastinal B-cell lymphoma (PMBCL) is the only non-Hodgkin’s lymphoma variant responding to immune checkpoint inhibitor (ICI) therapy, approximately in half of the cases; however, no molecular markers predicting a response to ICI therapy in PMBCL have been described so far. In this study, we assessed the incidence of the loss of heterozygosity (LOH), elevated microsatellite alteration at selected tetranucleotides (EMAST), and microsatellite instability (MSI) in the tumor genomes of 72 patients with PMBCL undergoing high-dose chemotherapy treatment at the National Research Center for Hematology (Moscow, Russia). Tumor DNA was isolated from biopsy samples taken at diagnosis. Control DNA was isolated from the blood of patients in complete remission or from buccal epithelium. STR-profiles for LOH and EMAST were assessed by PCR with COrDIS Plus multiplex kit (Gordiz Ltd., Moscow, Russia). LOH was detected in 37 of 72 patients (51.4%). EMAST was found in 40 patients (55.5%); 24 had a combination of EMAST with LOH. MSI-high was not found, while MSI-low was detected only in one patient. The association of certain genetic lesions with the clinical outcome in patients receiving treatment according to the standard clinical protocol R-Da-EPOCH-21 has been estimated (58 patients out of 72) and no associations with the worst overall or event-free survival were found. Full article

We used a real-world database (GuardantINFORM^TM) to analyze the treatment choices for patients with mCRC who underwent next-generation sequencing of circulating tumor DNA (ctDNA) using a commercially available test (Guardant360^®) after first- or second-line therapy. From 18,875 patients with claims for CRC, 1064 had confirmed metastatic disease and sufficient histories for analysis (median age 59 years, 44.8% female, 44.5% left-sided). ctDNA was detectable for 997/1064 (93.7%) patients. Clinically actionable molecular profiles were present for 507/1064 (47.7%) patients, including those who had not received targeted therapy in the previous line (410/926, 44.3%). Second- or third-line targeted therapies were administered to 338/1064 patients (31.8%) and were considered matched for 193/338 (57.1%) patients. Therapies administered after testing were informed by the ctDNA results in 56.7% of patients overall (603/1064). Time to treatment discontinuation was most favorable for patients with a clinically actionable ctDNA profile who received matched therapy. This analysis demonstrates the real-world clinical value of plasma-based comprehensive genomic profiling for selecting appropriate molecular-targeted therapies in mCRC patients with disease progression after first- or second-line therapy. Full article

The role of inflammatory responses in predicting outcomes in oncological thoracic surgery is still unclear. The aim of this study was to evaluate a series of blood count inflammation indexes as predicting factors for postoperative complications. We retrospectively studied 249 patients undergoing elective thoracic surgery in our institution between 2008 and 2020. A total of 184 patients underwent open surgery, and 65 underwent VATS. The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios, Systemic Inflammation Response Index (SIRI) were calculated preoperatively and on the first and fourth postoperative days, as well as a new derivative index, the Aggregate Inflammation Systemic Index (AISI). Univariate correlations evidenced a statistically significant association between the NLR at the fourth postoperative day and the occurrence of surgical complications in the global cohort (rho = 0.15, p = 0.03). A similar significant association with MLR on the fourth postoperative day is found in the open group (rho = −0.15, p = 0.048). NLR and LMR on the fourth postoperative day are associated with postoperative complications in the whole and open groups, respectively. Simple, easy-to-perform and inexpensive, blood cell count indexes may be useful in predicting complications in oncological thoracic surgery. A greater number of broader, prospective, randomized studies are necessary to confirm these findings. Full article

Background: Health economic evaluations are needed to assess the impact on the healthcare system of emerging treatment patterns for advanced prostate cancer. The objective of this study is to review the scientific literature identifying cost-effectiveness and cost analyses that are assessing treatments for metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). Methods: On 29 June 2021, we searched the scientific (MEDLINE, Embase, and EBSCO) and grey literature for health economic studies targeting mHSPC and nmCRPC. We used the CHEC-extended checklist and the Welte checklist for risk-of-bias assessment and transferability analysis, respectively. Results: We retained 20 cost-effectiveness and 4 cost analyses in the mHSPC setting, and 14 cost-effectiveness and 6 cost analyses in the nmCRPC setting. Docetaxel in combination with androgen deprivation therapy (ADT) was the most cost-effective treatment in the mHSPC setting. Apalutamide, darolutamide, and enzalutamide presented similar results vs. ADT alone and were identified as cost-effective treatments for nmCRPC. An increase in costs as patients transitioned from nmCRPC to mCRPC was noted. Conclusions: We concluded that there is an important unmet need for health economic evaluations in the mHSPC and nmCRPC setting incorporating real-world data to support healthcare decision making. Full article

The aim of this monocentric, retrospective clinical study was to evaluate the status of osseous union in uni- and poly-segmental mandible reconstructions regarding conventional angle-stable manually bent osteosynthesis plates (Unilock 2.0 mm) versus titan laser-melted PSI patient-specific implant’s (PSI). The clinical impact of PSI’s high stiffness fixation methods on bone healing and regeneration is still not well addressed. The special interest was in evaluating the ossification of junctions between mandible and fibula and between osteotomized fibula free flap (FFF) segments. Panoramic radiograph (OPT), computed tomography (CT) scans, or cone-beam CTs (CBCT) of patients who underwent successful FFF for mandible reconstruction from January 2005 to December 2020 were analyzed. A total number of 89 cases (28 females (31.5%), 61 males (68.5%), mean age 58.2 ± 11.3 years, range: 22.8–82.7 years) fulfilled the chosen inclusion criteria for analysis (conventional: n = 44 vs. PSI: n = 45). The present study found an overall incomplete ossification (IOU) rate of 24.7% (conventional: 13.6% vs. PSI: 35.6%; p = 0.017) for mandible to fibula and intersegmental junctions. Between osteotomized FFF segments, an IOU rate of 16% was found in the PSI-group, while no IOU was recorded in the conventional group (p = 0.015). Significant differences were registered for IOU rates in poly-segmental (p = 0.041), and lateral (p = 0.016) mandibular reconstructions when PSI was used. Multivariate logistic regression analysis identified plate exposure and type of plate used as independent risk factors for IOU. Previous or adjuvant radiotherapy did not impact incomplete osseous union in the evaluated study sample. PSI is more rigid than bent mini-plates and shields functional mechanical stimuli, and is the main reason for increasing the rate of incomplete ossification. To enhance the functional stimulus for ossification it has to be discussed if patient-specific implants can be designed to be thinner, and should be divided into segmental plates. This directs chewing forces through the bone and improves physiological bone remodeling. Full article