Seminars In Oncology[JOURNAL]
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200 papers
Cancer stage and time from cancer diagnosis to first treatment during the COVID-19 pandemic.
Mendonça E Silva DR, Fernandes GA, França E Silva ILA … +1 more , Curado MP
Semin Oncol · 2023 · PMID 37005143 · Full text
The 2019 coronavirus disease (COVID-19) pandemic has impacted cancer care and the diagnosis of new cases of cancer. We analyzed the impact of the COVID-19 pandemic on patients with cancer by comparing the number of newly...
The 2019 coronavirus disease (COVID-19) pandemic has impacted cancer care and the diagnosis of new cases of cancer. We analyzed the impact of the COVID-19 pandemic on patients with cancer by comparing the number of newly diagnosed cases, cancer stage, and time to treatment in 2020 with those in 2018, 2019, and 2021. A retrospective cohort of all cancer cases treated at A.C. Camargo Cancer Center in 2018-2021, identified from the Hospital Cancer Registry, was studied. We analyzed single and multiple primary cancer case and patient characteristics-by year and by clinical stage (early v advanced). Times from diagnosis to treatment were compared according to the most frequent tumor sites between 2020 and the other study years. Between 2018 and 2021, a total of 29,796 new cases were treated at the center including 24,891 with a single tumor and 4,905 with multiple tumors, including nonmelanoma skin cancer. The number of new cases decreased by 25% between 2018 and 2020 and 22% between 2019 and 2020, followed by an increase of about 22% in 2021. Clinical stages differed across years, with the number of new advanced cases decreasing from 17.8% in 2018 to 15.2% in 2020. Diagnoses of advanced-stage for lung and kidney cancer decreased between 2018 and 2020, while the number of thyroid and prostate cancer cases diagnosed in advanced-stages increased from 2019 to 2020. The time from diagnosis to treatment decreased between 2018 and 2020 for breast (55.5 v 48 days), prostate (87 v 64 days), cervical/uterine (78 v 55 days) and oropharyngeal (50 v 28 days) cancers. The COVID-19 pandemic affected the numbers of single and multiple cancers diagnosed in 2020. An increase in the number of advanced-stage cases diagnosed was observed only for thyroid and prostate cancer. This pattern may change in coming years due to the possibility that a significant number of cases went undiagnosed in 2020.
Battling chronic myeloid leukemia in a resource-constrained country: A case of public-private partnerships.
Tariq R, Fatima I, Shahid MH … +3 more , Tariq S, Niaz F, Hussain SM
Semin Oncol · 2023 · PMID 37005142 · Publisher ↗
Pakistan, where chronic myeloid leukemia constitutes around 80% of all myeloproliferative disorders, has been exploring multiple avenues in order to ensure the accessibility and affordability of imatinib and nilotinib. W...
Pakistan, where chronic myeloid leukemia constitutes around 80% of all myeloproliferative disorders, has been exploring multiple avenues in order to ensure the accessibility and affordability of imatinib and nilotinib. While most provinces of the country have joined hands with a pharmaceutical company to dispense free anti-CML medicines as part of a public-private partnership, the patients are still facing numerous challenges in the form of geographical disparity in the availability of these medicines, other out-of-pocket expenditures and most importantly, the uncertainty associated with the long-term continuation of this public-private endeavor due to procedural delays. In light of these predicaments, channeling resources towards research and development, fostering partnerships between government and NGOs and tapping into the domain of compulsory licensing appear to be the most sustainable solutions.
Non-pharmacologic interventions for improving cancer-related fatigue (CRF): A systematic review of systematic reviews and pooled meta-analysis.
Belloni S, Arrigoni C, Baroni I … +6 more , Conte G, Dellafiore F, Ghizzardi G, Magon A, Villa G, Caruso R
Semin Oncol · 2023 · PMID 36973125 · Publisher ↗
INTRODUCTION: Literature encloses numerous systematic reviews (SRs) on nonpharmacologic interventions for improving cancer-related fatigue (CRF). The effect of these interventions remains controversial, and the available...
INTRODUCTION: Literature encloses numerous systematic reviews (SRs) on nonpharmacologic interventions for improving cancer-related fatigue (CRF). The effect of these interventions remains controversial, and the available SRs have not been synthesized yet. We conducted a systematic synthesis of SRs and meta-analysis to determine the effect of nonpharmacologic interventions on CRF in adults. MATERIAL AND METHODS: We systematically searched 4 databases. The effect sizes (standard mean difference) were quantitatively pooled using a random-effects model. Chi-squared (Q) and I-square statistics (I²) tested the heterogeneity. RESULTS: We selected 28 SRs, including 35 eligible meta-analyses. The pooled effect size (standard mean difference, 95% CI) was -0.67 (-1.16, -0.18). The subgroup analysis by types of interventions showed a significant effect in all the investigated approaches (complementary integrative medicine, physical exercise, self-management/e-health interventions). CONCLUSIONS: There is evidence that nonpharmacologic interventions are associated with CRF reduction. Future research should focus on testing these interventions on specific population clusters and trajectories. PROSPERO REGISTRATION: CRD42020194258.
Improved outcomes in women with BRAF-mutant melanoma treated with BRAF/MEK-targeted therapy across randomized clinical trials. A systematic review and meta-analysis.
Pala L, De Pas T, Pagan E … +14 more , Minucci S, Catania C, Digiacomo N, Cocorocchio E, Laszlo D, Di Muzio A, Barigazzi C, Stucchi E, De Grandi L, Stucchi S, Viale G, Gelber RD, Bagnardi V, Conforti F
Semin Oncol · 2023 · PMID 36967333 · Publisher ↗
Available evidence suggests that in patients with advanced BRAF V600-mutant melanoma treated with the combination of BRAF and MEK inhibitors, gender could be associated with survival outcome. We performed a systematic re...
Available evidence suggests that in patients with advanced BRAF V600-mutant melanoma treated with the combination of BRAF and MEK inhibitors, gender could be associated with survival outcome. We performed a systematic review and meta-analysis of all randomized clinical trials (RCTs) testing the combination of BRAF and MEK inhibitors, to assess the interaction between treatment effect and patients' gender. We searched PubMed, MEDLINE, Embase, and Scopus, for phase II and III RCTs up to January 30, 2022. We included all RCTs that enrolled patients with BRAF V600-mutant advanced cutaneous melanoma and assessed combinations of BRAF and MEK inhibitors versus BRAF inhibitor monotherapy. Our aim was to assess differences if any in treatment efficacy between men and women, measured in terms of the differences in progression-free survival (PFS) and overall survival (OS) log-hazard ratios (log-HRs). We calculated the pooled PFS- and OS-HRs with 95% confidence intervals (CIs) in men and women using a random-effects model and assessed the heterogeneity between the estimates using an interaction test. Five RCTs that enrolled a total of 2,113 patients were included in the analysis. In women, the combination of BRAF and MEK inhibitors halved the risk of progression or death as compared with BRAF inhibitor monotherapy with a pooled PFS-HR of 0.50 (95%CI 0.41-0.61). In men, the benefit obtained with BRAF and MEK inhibitors was smaller with a pooled PFS-HR of 0.63 (95%CI 0.54-0.74), P-heterogeneity = .05. A similar trend was observed for OS where the pooled OS-HR was 0.62 (95%CI 0.48-0.80) in women and only 0.78, (95%CI 0.67-0.92) in men, P-heterogeneity = 0.11. These results support meaningful gender-based heterogeneity of response to combination of BRAF and MEK inhibitors targeted therapy in patients with advanced BRAF-mutant melanoma, that should be considered in future research to improve treatment effectiveness.
From doctors to ancillary staff: Regional and metropolitan cancer workforce perceptions and distress resulting from COVID-19 pandemic adaptations.
Roberts NA, Ahern E, Pelecanos A … +3 more , Gasper H, Chan B, Lwin Z
Semin Oncol · 2022 Dec · PMID 36797193 · Full text
INTRODUCTION: The declaration of the COVID-19 pandemic has resulted in necessary and rapid changes to health service delivery. In the Australian context, it has been broadly identified that these impacts have been felt b...
INTRODUCTION: The declaration of the COVID-19 pandemic has resulted in necessary and rapid changes to health service delivery. In the Australian context, it has been broadly identified that these impacts have been felt by health care workers (HCW) providing care. We aimed to capture oncology HCW perceptions of support, stress, personal ability to meet needs and institutional preparedness across longitudinal periods of COVID-19 response in the early stages of the pandemic. METHODS AND MATERIALS: An electronic survey was developed to measure the weekly impacts and distress experienced by HCW during the early phases of the pandemic. Hospital email communications relating to pandemic directives were noted. HCW included nursing, medical, ancillary staff and allied health team members at 2 study sites, 1 metropolitan and 1 regional center in Queensland, Australia. Descriptive statistics were applied to quantitative data, and a framework analysis for qualitative data. Key themes were synthesized using mixed methods approaches. RESULTS: A total of 176 HCW consented to participate. Four key themes were identified. Key theme 1 was strategies for protection, and included the subthemes of self-isolation, using personal protective equipment (PPE), protecting patients and families and each other. Key theme 2 was navigating rules and keeping up, and included the subthemes of compliance, exceptions, conflict and complex decision fatigue. Key theme 3 was tempered optimism, with subthemes including this is grief, pride in one's place and strategies for coping. Key theme 4 was framing the new normal, with subthemes including using technology, second wave and uncertainty. CONCLUSION: Staff groups reported the emotional impacts of rapid change across clinical areas and centers. Distress corresponded to rapid change amid uncertainty, rather than reported infection rates. These findings give insight into the experiences of patient facing oncology HCW during periods of uncertainty, potentially informing policy in the future.
Is the neutrophil-to-lymphocyte ratio a prognostic factor in non-small cell lung cancer patients who receive adjuvant chemotherapy?
Smith D, Raices M, Cayol F … +3 more , Corvatta F, Caram L, Dietrich A
Semin Oncol · 2022 Dec · PMID 36775797 · Publisher ↗
Inflammation plays a key role in malignant tumor progression. Neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and, as such, high isolated pretreatment NLR has been shown in some studies to be as...
Inflammation plays a key role in malignant tumor progression. Neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and, as such, high isolated pretreatment NLR has been shown in some studies to be associated with worse long-term outcomes. We summarize the data regarding the utility of NLR as a prognosis factor and present results of a single institution study assessing the usefulness of high preoperative NLR as a prognosis factor for patients with successfully resected NSCLC who receive adjuvant cisplatin-based chemotherapy. While largely supportive of the value of NLR as a prognostic factor, the literature is not consistent and suggest a more nuanced association. Our single institution study adds to the exiting literature. We conclude preoperative NLR can be used as a reliable, cost-effective biomarker to estimate prognosis in NSCLC patients who have undergone lung lobectomy with curative intent followed by cisplatin-based adjuvant chemotherapy.
Airway disorders associated with immune checkpoint inhibitor therapy: Two case reports and a systematic review.
Kawakami N, Saito H, Takahashi S … +6 more , Kajie S, Kato R, Shimaya K, Wakai Y, Saito K, Sakashita M
Semin Oncol · 2022 Dec · PMID 36759235 · Publisher ↗
Immune checkpoint inhibitors (ICI) are widely used for the treatment of various malignant neoplasms. Interstitial lung disease is a well-known immune-related adverse event, however, ICI-induced airway disease remains und...
Immune checkpoint inhibitors (ICI) are widely used for the treatment of various malignant neoplasms. Interstitial lung disease is a well-known immune-related adverse event, however, ICI-induced airway disease remains under-recognized. Herein, we report two similar cases of pembrolizumab-induced tracheobronchitis presenting as persistent chronic cough and dyspnea. Blood tests revealed elevated C-reactive protein levels without eosinophilia. Spirometry demonstrated mild airflow obstruction. Computed tomography revealed diffuse thickening of the tracheobronchial walls and bronchiectasis predominantly in the lower lobes. Bronchoscopy revealed edematous and erythematous tracheobronchial mucosa, and bronchial biopsy tissue exhibited marked inflammation with predominant infiltration of CD8+ lymphocytes. Subsequently, pembrolizumab-induced tracheobronchitis was diagnosed in both cases. Cessation of pembrolizumab and initiation of erythromycin, inhaled corticosteroids, and long-acting beta-agonists gradually improved the symptoms, airflow obstruction, and radiographic findings. These were completely resolved in one case. The other case initially showed a poor response to systemic corticosteroids combined with the aforementioned drugs, but improved gradually and almost completely. These cases exemplify ICI-induced airway disease that is, an under-recognized manifestation of immune-related adverse events. In addition, we have systematically searched the PubMed database for articles on ICI-induced airway disease, categorized the retrieved articles as eosinophilic and non-eosinophilic airway diseases, and reviewed the differences in treatment and prognoses between these two categories.
Synchronous or metachronous presentation of pancreatic neuroendocrine tumor versus secondary lesion to pancreas in patients affected by renal cell carcinoma. Systematic review.
Persano I, Parlagreco E, La Salvia A … +5 more , Audisio M, Volante M, Buttigliero C, Scagliotti GV, Brizzi MP
Semin Oncol · 2022 Dec · PMID 36759234 · Publisher ↗
The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). These two mal...
The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). These two malignancies share both radiological and cytopathological features, making the differential diagnosis very challenging. In this review, we collected all cases of concurrent diagnosis of localized panNET and RCC, with or without VHL, as reported in the literature to date. We aimed to provide an insight into the differential diagnosis between panNET and RCC pancreatic metastasis with a focus on the optimal therapeutic algorithm depending on the diagnosis. We performed literature research in PubMed library databases for articles about coexisting panNET and RCC published from 2001 to 2018. We selected nine articles with a total of 13 patients, including one treated at our institution. Patients' median age was 49 years and eight out of 13 patients were women. VHL was diagnosed in nine cases. Most patients underwent radical nephrectomy for RCC (9/13) and a clear cell renal carcinoma variant was identified in six cases. The diagnosis of panNET was synchronous with RCC detection in nine cases and metachronous in four cases. The diameter of the pancreatic lesion was >2 cm in six cases. In two cases the panNET was misdiagnosed as metastatic RCC by radiological tests. Somatostatin receptor scanning was performed only in our patient (Octreoscan) showing intense uptake in the pancreatic mass. Endoscopic ultrasound fine needle aspiration of the pancreatic lesion was performed in four patients: in two cases the panNET was confused with metastatic RCC by cytological analysis. Most patients underwent pancreatic surgery (10/13) without histological confirmation. Clear cell panNET was recognized in six cases, while mixed neuroendocrine non-neuroendocrine neoplasm was diagnosed in one patient. Immunohistochemistry (IHC) staining showed positivity to typical neuroendocrine markers (chromogranin A and synaptophysin) in all reported tested cases (8/8). Three patients underwent systemic treatment: two patients received sunitinib and one patient interleukin-2 (IL-2). Other neoplasms were observed in seven patients, of whom six were affected by VHL syndrome. When neoplastic lesions are recognized in both the kidney and pancreas, panNET and RCC pancreatic metastasis are often misdiagnosed due to similar radiological and cytopathological features. An accurate differential diagnosis is crucial and IHC plays a central role in distinguishing the two entities. The therapeutic algorithm may change depending on the diagnosis: while pancreatic RCC metastases benefit from resection, in panNETs and VHL the indication for surgery must be carefully evaluated.
The challenges of selecting cancer medicines for the WHO Essential Medicines List with the elephant in the room: A path forward.
Fojo T
Semin Oncol · 2022 Dec · PMID 36754713 · Publisher ↗
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Predictors of treatment refusal in patients with colorectal cancer: A systematic review.
Moodley Y, Govender K, van Wyk J … +10 more , Reddy S, Ning Y, Wexner S, Stopforth L, Bhadree S, Naidoo V, Kader S, Cheddie S, Neugut AI, Kiran RP
Semin Oncol · 2022 Dec · PMID 36754712 · Full text
This systematic review was conducted to investigate predictors of treatment refusal in colorectal cancer (CRC) patients. An understanding of these predictors would inform statistical models for the identification of high...
This systematic review was conducted to investigate predictors of treatment refusal in colorectal cancer (CRC) patients. An understanding of these predictors would inform statistical models for the identification of high-risk patients who might benefit from interventions that seek to improve treatment compliance. We performed a search of PubMed and Scopus to identify potentially relevant studies on predictors of treatment refusal in CRC patients that were published between January 1, 2000 and December 31, 2021. We screened manuscripts using predefined eligibility criteria. Information on study design, study location, patient characteristics, treatments, rates and predictors of treatment refusal, and the impact of treatment refusal on mortality or survival were collected from eligible studies. Study quality was assessed using the Newcastle-Ottawa score. The overall findings of the review process were summarized using descriptive statistics and a narrative synthesis. A total of 13 studies were included in this review. Ten studies reported on refusal of CRC surgery, refusal rate: 0.25%-3.26%; three studies reported on chemotherapy refusal (one of which reported on both surgery and chemotherapy refusal), refusal rate: 7.8%-41.5%; and one study reported on refusal of any cancer treatment, refusal rate: 8.7%. The bulk of the published literature confirmed the harmful association between treatment refusal and poor survival outcomes in CRC patients. Frequently cited predictors of treatment refusal included patient demographic characteristics (age, race, gender), clinical characteristics (disease stage, comorbidity), and factors that impact access to cancer care services (healthcare insurance, facility level). Potentially high rates of treatment refusal pose a challenge to CRC control. This review has identified several factors which must be considered when attempting to reduce treatment refusal in CRC patients. Furthermore, these factors should be tested as components of predictive risk models for this important outcome.
A narrative review of the principal glucocorticoids employed in cancer.
Denaro N, Garrone O, Morelli A … +9 more , Pellegrino B, Merlano MC, Vacca D, Pearce J, Farci D, Musolino A, Scartozzi M, Tommasi C, Solinas C
Semin Oncol · 2022 Dec · PMID 36737303 · Publisher ↗
Glucocorticoids (GCs) are a pharmacological class of drugs widely used in oncology in both supportive and palliative settings. GCs differentially impact organs with immediate and long-term effects; with suppressive effec...
Glucocorticoids (GCs) are a pharmacological class of drugs widely used in oncology in both supportive and palliative settings. GCs differentially impact organs with immediate and long-term effects; with suppressive effect on the immune system anchoring their use to manage the toxicities of immune checkpoint inhibitors (ICIs). In addition, GCs are often used in the management of symptoms related to cancer or chemotherapy and as adjuvants in the treatment of pain in the management of other. In the palliative setting, GCs, especially administered subcutaneously can be to assist in the control of nausea, dyspnea, asthenia, and anorexia-cachexia syndrome. In this narrative review, we aim to summarize the role of GCs in the different settings (curative, supportive, and palliative) to help clinicians use these important drugs in their daily clinical practice with cancer patients.
Dexamethasone to prevent everolimus-induced stomatitis (Alliance MIST Trial: A221701).
Ruddy KJ, Zahrieh D, He J … +11 more , Waechter B, Holleran JL, Lewis LD, Chow S, Beumer J, Weiss M, Trikalinos N, Faller B, Lustberg M, Rugo HS, Loprinzi C
Semin Oncol · 2023 · PMID 36693773 · Full text
mTOR inhibitors such as everolimus may cause oral stomatitis, often a dose-limiting toxicity. Prior clinical research has suggested that a dexamethasone mouth rinse might help prevent and/or treat this. Alliance A221701...
mTOR inhibitors such as everolimus may cause oral stomatitis, often a dose-limiting toxicity. Prior clinical research has suggested that a dexamethasone mouth rinse might help prevent and/or treat this. Alliance A221701 was a randomized phase III trial of patients initiating 10 mg daily oral everolimus that compared dexamethasone mouthwash taken preventively (initial dexamethasone group) versus therapeutically (initial placebo group) to assess two coprimary endpoints: the incidence of mTOR inhibitor-associated stomatitis (mIAS), and the area under the curve (AUC) of mIAS-associated pain over an 8-week treatment period. A Fisher's exact test was used to compare the incidences while a Wilcoxon rank-sum test was used to compare the AUCs. In addition, we performed an exploratory analysis of the association of everolimus trough concentrations and toxicity using a Mann-Whitney U test. Due to slow accrual, this study closed after 39 patients were randomized (19 to upfront placebo and 20 to upfront dexamethasone). There were no significant differences between groups seen in either of the coprimary endpoints; furthermore, we found no association between whole blood everolimus trough concentrations and toxicity. Although limited by poor enrollment, the results of this study do not suggest that prophylactic dexamethasone mouthwash is superior to therapeutic dexamethasone mouthwash (initiated at the first sign of mouth pain) for reducing the incidence or severity of mIAS from everolimus.
Prevalence, mutational spectrum and clinical implications of clonal hematopoiesis of indeterminate potential in plasma cell dyscrasias.
Testa S, Kumar J, Goodell AJ … +6 more , Zehnder JL, Alexander KM, Sidana S, Arai S, Witteles RM, Liedtke M
Semin Oncol · 2022 Dec · PMID 36503855 · Publisher ↗
Clonal hematopoiesis of indeterminate potential (CHIP) is common both in healthy individuals and patients with hematological cancers. Recent studies have showed worse prognosis for patients with multiple myeloma (MM) and...
Clonal hematopoiesis of indeterminate potential (CHIP) is common both in healthy individuals and patients with hematological cancers. Recent studies have showed worse prognosis for patients with multiple myeloma (MM) and non-Hodgkin lymphoma undergoing stem cell transplant, that have concomitant presence of CHIP. Data regarding the clinical and biological role of CHIP in plasma cell dyscrasias (PCDs) is rapidly increasing. However, the prevalence and prognostic implication of CHIP in patients with MM outside of the transplant setting, and in those with other more indolent PCDs remains elusive. Here we explored the prevalence and clinical implications of CHIP detected through next-generation sequencing in 209 patients with PCDs including MM, light chain (AL) amyloidosis (ALA), monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM). To avoid attributing the mutations to the plasma cell clone, CHIP was defined as the presence of DNMT3A, TET2, or ASXL1 mutations in the peripheral blood or bone marrow (DTA-CH). The prevalence of DTA-CH was 19% in patients with PCDs, with no difference between each PCD. TET2 (23%) and DNMT3A (22%), were the most frequently mutated genes. DTA-CH correlated with older age in MM (P = .001) and MGUS/SMM (P = 0.0007), as well as with coronary artery disease or congestive heart failure in MM (P = .03). DTA-CH did not predict worse OS or PFS in either MM or ALA, nor it predict higher risk of progression to MM in patients with MGUS/SMM. Our results overall further elucidate the prevalence and mutational spectrum of CHIP in PCDs, providing more information regarding the clinical relevance of CHIP in this patient population.
IO-IO vs IO-TKI efficacy in metastatic kidney cancer patients: A structured systematic review over time.
Hoeh B, Flammia RS, Hohenhorst L … +17 more , Sorce G, Panunzio A, Tappero S, Tian Z, Saad F, Gallucci M, Briganti A, Terrone C, Shariat SF, Graefen M, Tilki D, Antonelli A, Kosiba M, Kluth LA, Becker A, Chun FKH, Karakiewicz PI
Semin Oncol · 2022 Oct · PMID 36333148 · Publisher ↗
Multiple systemic immune-oncology (IO) combination therapies have demonstrated overall survival (OS) benefits in metastatic renal clear cell carcinoma (mRCC). However, the magnitude of benefits over time has not been com...
Multiple systemic immune-oncology (IO) combination therapies have demonstrated overall survival (OS) benefits in metastatic renal clear cell carcinoma (mRCC). However, the magnitude of benefits over time has not been compared in a structured fashion. To assess OS and progression free survival (PFS) efficacy as reflected by hazard ratios [HR]) according to the duration of follow-up over time for each of four IO combination therapies. A systematic PubMed (MEDLINE) literature review was performed (January, 1, 2016 to February, 20, 2022). Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included. These search criteria yielded four eligible RCTs: CheckMate 214 (nivolumab plus ipilimumab), Keynote 426 (pembrolizumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib), CLEAR (lenvatinib plus pembrolizumab). OS and PFS HRs were tabulated for all four studies including all reported timepoints. Median follow-up ranged from 25-68 months for CheckMate 214 (5 timepoints), 13-43 months for Keynote 426 (3 timepoints), 18-33 months for CheckMate 9ER (3 timepoints) and 27-34 months for CLEAR (2 timepoints). Respective OS and PFS HRs were 0.68-0.72 and 0.98-0.86, 0.53-0.73 and 0.69-0.68, 0.60-0.70 and 0.51-0.56, 0.66-0.72 and 0.39-0.47 for CheckMate 214, Keynote 426, CheckMate 9ER and CLEAR. Regarding OS HRs virtually no change was recorded over time for CheckMate 214, but a decrease in magnitude occurred in the three IO-TKI remaining studies. Regarding PFS HRs, no benefit was recorded for CheckMate 214. Statistically significant benefit was recorded in the remaining IO-TKI studies. However, it also decreased with longer follow-up. It remains to be seen, whether further 'slippage' of efficacy will persist as the data matures further for all IO-TKI combinations.
Which future for de-intensified treatments in HPV-related oropharyngeal carcinoma?
Cavalieri S, Nuzzolese I, Licitra L
Semin Oncol · 2022 Oct · PMID 36241485 · Publisher ↗
The development of deintensified therapies aiming at reducing the treatment-related toxicity while not impairing the outcome is an unmet need in HPV+ oropharyngeal carcinoma patients. Several deintensification approaches...
The development of deintensified therapies aiming at reducing the treatment-related toxicity while not impairing the outcome is an unmet need in HPV+ oropharyngeal carcinoma patients. Several deintensification approaches have been explored in this setting, including induction chemotherapy with reduced chemoradiation dose in responding pts. The findings of the studies conducted so far show that the available deescalated therapy should be based on the disease risk profile. At present, we still lack robust high level data to infer that the cited interventions are equivalent or superior to standard of care treatments. However, literature data suggest that approximately 70% of low-risk patients might receive a deintensified approach by including either surgery or induction chemotherapy. In the context of high-risk disease, more than 80% of patients may undergo a deintensified loco-regional treatment by neoadjuvant systemic therapy. Epidemiological data suggest that in the next decades, most of the HPV-related OPSCC patients will be made of old and possibly frail individuals. However, this patient population was excluded from most of the studies conducted so far. Therefore, there is a strong need for clinical trials to define risk-based deescalation strategies in this population and in younger patients as well.
Impact of the COVID-19 Pandemic on the Wellbeing of International Oncology and Hematology Fellows at the Princess Margaret Cancer Center (PMCC).
Stecca CE, Alt M, Jiang DM … +5 more , Michelis G, Fallah-Rad N, Gill S, Elliot M, Sridhar SS
Semin Oncol · 2022 Oct · PMID 36210226 · Full text
BACKGROUND: The COVID-19 pandemic has led to significant disruptions across all levels of medical training. International fellows in subspecialty training programs are essential members of the frontline physician workfor...
BACKGROUND: The COVID-19 pandemic has led to significant disruptions across all levels of medical training. International fellows in subspecialty training programs are essential members of the frontline physician workforce, but may face additional and unique challenges as a result of being away from their home country. In this study, we aimed to understand the impact of the COVID-19 pandemic on the wellbeing of international fellows in the Hematology and/or Oncology fellowship program at the PMCC. METHODS: In collaboration with our staff psychiatrist, we conducted an online survey of hematology and/or oncology fellows at the PMCC from July 6 to August 10, 2020. The survey consisted of 60 questions divided into 4 sections: demographics, wellbeing assessment using the validated Short Warwick Edinburgh Mental Wellbeing Scale (SWEMWBS), fellowship specific questions (personal and professional) and coping strategies using the validated brief COPE scale. RESULTS: Overall 24/52 (46%) fellows completed the survey: 21/24 were international fellows with 48% from Asia, 3/24 were Canadian fellows but away from home; 54% were male; 48% were aged 31-35 years; 65% were married, 48% had children. Mean SWEMWBS score was 21, indicating lower overall wellbeing than the general population who had a score of 23.6. Compared to their pre-COVID status, many reported a decline in their wellbeing (63%), sense of guilt for not being with their family (45%) or helping their country (41%), stress in personal relationships (26%), fatigue (50%), sleep disorders (38%) and loss of interest in daily activities (38%). Personal events were altered by almost 80%; and 20% planned to extend their fellowship. According to the Brief-COPE scale, during the pandemic, most fellows used more adaptive coping mechanisms (mean score 39.2) as opposed to maladaptive ones (mean score 21.8). CONCLUSIONS: The ongoing COVID-19 pandemic has negatively affected the overall wellbeing of international fellows. Understanding the specific challenges and coping mechanisms used by international fellows may help institutions develop better targeted strategies to promote wellbeing, professional development and ensure high-quality patient care during unprecedented times like the COVID pandemic.
A systematic review and meta-analysis on non-metastatic castration resistant prostate cancer: The radiation oncologist's perspective.
Ingrosso G, Bottero M, Becherini C … +12 more , Caini S, Alì E, Lancia A, Ost P, Sanguineti G, Siva S, Zilli T, Francolini G, Bellavita R, Aristei C, Livi L, Detti B
Semin Oncol · 2022 Oct · PMID 36192243 · Publisher ↗
Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic option is androgen deprivation: despite initial respons...
Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic option is androgen deprivation: despite initial response rates, a progression to a state of castration resistance is observed in most of the patients. In the present article, we conducted a systematic review and meta-analysis of all clinical trials assessing treatment for nmCRPC with next-generation androgen receptor inhibitors. We performed a review and meta-analysis of phase III randomized controlled trials comparing new agents (apalutamide, enzalutamide, darolutamide) with placebo as control arm, in the setting of nmCRPC. Patients treated with next-generation ARIs had a 26% reduction in the risk of death compared with placebo; compared with other ARIs, darolutamide had the lowest rate of grade 3 and 4 AEs and the lowest therapy discontinuation rate due to any grade AEs. This meta-analysis shows that treatment with new ARIs is safe and significantly reduces the risk of death and of metastasis onset in nmCRPC patients. Under way studies on new biomarkers such as genomic classifiers will probably allow the stratification in more specific subsets of disease. New imaging modalities such as PSMA-PET have shown greater sensibility and specificity than conventional imaging in metastases detection. All patients were randomized in a 2:1 fashion, with a total of 2,694 who underwent next-generation ARIs (806 apalutamide, 955 darolutamide, 933 enzalutamide) and 1,423 in the placebo arm.
Under-representation of women in Randomized Clinical Trials testing anticancer immunotherapy may undermine female patients care. A call to action.
Pala L, De Pas T, Conforti F
Semin Oncol · 2022 Oct · PMID 36192242 · Publisher ↗
Immunotherapy with immune-checkpoint inhibitors (ICIs) has revolutionized the landscape of cancer treatment, dramatically improving the prognosis of patients with several solid tumors. Sex and gender are variables that a...
Immunotherapy with immune-checkpoint inhibitors (ICIs) has revolutionized the landscape of cancer treatment, dramatically improving the prognosis of patients with several solid tumors. Sex and gender are variables that affect immune responses to both foreign and self-antigens and growing preclinical and clinical evidence show that they also affect efficacy and tolerability of anticancer immunotherapy in patients with several advanced solid tumors. Despite such strong biological rationale and available evidence highlighting the need to take into account sex-based differences in the context of both research and clinical practice for anticancer immunotherapy, we described here an impressive under-representation of women enrolled in randomized clinical trials (RCTs) testing such drugs over the last 10 years. We critically discuss limitations the under-representation of women has on the generalization of results of RCTs to female patients, as well as the importance in the future of ensuring increased enrollment of women in trials, including sex as stratifying factor in trials design, and guaranteeing sex-specific analysis of efficacy and safety results, in order to avoid less than optimal treatment of women with cancer.
Maintenance or consolidation therapy in small-cell lung cancer: an updated systematic review and meta-analysis.
Belluomini L, Pilotto S, Avancini A … +9 more , Insolda J, Sposito M, Menis J, Ciccarese C, Iacovelli R, Ferrara MG, Milella M, Bria E, Rossi A
Semin Oncol · 2022 Oct · PMID 36184311 · Publisher ↗
We performed an updated meta-analysis to explore the role of maintenance therapy in SCLC. Clinical trials with randomization to maintenance/consolidation (V) placebo or observation or best supportive care in SCLC, both e...
We performed an updated meta-analysis to explore the role of maintenance therapy in SCLC. Clinical trials with randomization to maintenance/consolidation (V) placebo or observation or best supportive care in SCLC, both extended and limited disease were searched from January 2009 to March 2022. The hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) with the relative 95% confidence interval (CI) were extracted from each study. Summary HR was calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. A total of 9 studies were identified. Neither PFS nor OS were improved with maintenance/consolidation (PFS: random-effect; HR 0.93; 95% CI 0.71-1.21; P=0.10; OS: fixed-effect; HR 0.98; 95% CI 0.89-1.08; P=0.14). Among the different strategies, immunotherapy maintenance showed a significantly decreased risk of progression (V)standard of care (random-effect; HR 0.80; 95% CI 0.66-0.97; P=0.03). The current updated meta-analysis did not demonstrate a benefit of maintenance/consolidation therapy in SCLC, with only a PFS benefit for immunotherapy approach.
Torticollis as a presenting symptom of pediatric CNS tumors: A systematic review.
Baklizi N, Raswoli M, Burges M … +2 more , Moreira DC, Qaddoumi I
Semin Oncol · 2022 Oct · PMID 36180292 · Publisher ↗
To assess the frequency of torticollis as a presenting symptom of pediatric CNS tumors and its impact on pre-diagnostic symptom intervals (PSIs) and patient outcomes. We performed a systematic review of studies reporting...
To assess the frequency of torticollis as a presenting symptom of pediatric CNS tumors and its impact on pre-diagnostic symptom intervals (PSIs) and patient outcomes. We performed a systematic review of studies reporting torticollis in children with various CNS tumors. We searched PubMed for studies published from January 1972 to March 2021 in English. Case reports were included in the analysis if the following criteria were met (1) torticollis was the presenting symptom secondary to a CNS tumor (2) children <18 years of age, (3) underwent imaging intervention and (4) outcome data provided. Of 1,365 relevant articles, 45 were eligible for analysis according to our inclusion criteria representing 95 patients. Two independent investigators extracted the data, and a third investigator arbitrated discrepancies. We found that 38.9% of CNS tumors exhibited torticollis as the only presenting symptom. PSI lengths ranged from 0 to 4 years (median, 5 months) for low-grade tumors, and patient age and PSI length were inversely associated. Of patients with low-grade tumors, 23.8% received physiotherapy, in contrast with 0% of patients with high-grade tumors. PSI length also increased for patients who received rehabilitation, and 39.3% and 7.1% of patients with high-grade and low-grade tumors, respectively, died of their disease. Patients with low-grade tumors and torticollis as a primary presenting symptom were more likely to have a prolonged PSI. Therefore, CNS tumors should be considered in the differential diagnosis of acquired torticollis in children.
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