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  1. Article ; Online: Immunotherapy and Radiation Therapy Sequencing in Breast Cancer: A Systematic Review.

    Verma, Saurav / Young, Sympascho / Boldt, Gabriel / Blanchette, Phillip / Lock, Michael / Helou, Joelle / Raphael, Jacques

    International journal of radiation oncology, biology, physics

    2024  Volume 118, Issue 5, Page(s) 1422–1434

    Abstract: Purpose: In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where ... ...

    Abstract Purpose: In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate and ultrahypofractionated schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at nonirradiated sites, an "abscopal effect." The amplification of antitumor immune response is used as the rationale behind the concomitant use of ICIs and RT. To date, there is a lack of literature on the optimal sequence, timing, dose/fractionation schema, and treated RT volumes with ICIs in patients with BC, especially in the era of ultrahypofractionation.
    Methods and materials: We conducted a systematic review to delineate the reported treatment details, safety, and efficacy of combining ICI and RT in patients with BC. PubMed, Embase, and Cochrane CENTRAL were searched between 2014 and 2023. Data were extracted to assess the details of ICIs/RT delivery, safety, and efficacy.
    Results: Of the 12 eligible studies, 9 involved patients with metastatic BC. Most studies were phase 1/2, had a small sample size (range, 8-28), and were heterogenous in patient population and reported outcomes. The combination was reported to be safe. We identified 1 study in the perioperative setting, which did a posthoc analysis of safety/efficacy of ICIs in the adjuvant setting with receipt and pattern of RT.
    Conclusions: In conclusion, there are limited data on the dose, timing, fractionation, and volumes of RT in both the adjuvant and metastatic setting in BC. Ongoing/future trials should collect and report such data on RT details, whenever RT is used in combination with ICIs.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/radiotherapy ; Immunotherapy/methods ; Dose Fractionation, Radiation ; Tumor Microenvironment
    Language English
    Publishing date 2024-01-07
    Publishing country United States
    Document type Systematic Review ; Journal Article ; Review
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2024.01.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Treatment and Mortality Following Cancer Diagnosis Among People With Non-affective Psychotic Disorders in Ontario, Canada: A Retrospective Cohort Study.

    Wootten, Jared C / Richard, Lucie / Lam, Melody / Blanchette, Phillip S / Solmi, Marco / Anderson, Kelly K

    Schizophrenia bulletin

    2024  

    Abstract: Background and hypothesis: People with psychotic disorders have a higher risk of mortality following cancer diagnosis, compared to people without psychosis. The extent to which this disparity is influenced by differences in cancer-related treatment is ... ...

    Abstract Background and hypothesis: People with psychotic disorders have a higher risk of mortality following cancer diagnosis, compared to people without psychosis. The extent to which this disparity is influenced by differences in cancer-related treatment is currently unknown. We hypothesized that, following a cancer diagnosis, people with psychotic disorders were less likely to receive treatment and were at higher risk of death than those without psychosis.
    Study design: We constructed a retrospective cohort of cases of non-affective psychotic disorder (NAPD) and a general population comparison group, using Ontario Health (OH) administrative data. We identified cases of all cancers diagnosed between 1995 and 2019 and obtained information on cancer-related treatment and mortality. Cox proportional hazards models were used to compare the probability of having a consultation with an oncologist and receiving cancer-related treatment, adjusting for tumor site and stage. We also compared the rate of all-cause and cancer-related mortality between the two groups, adjusting for tumor site.
    Study results: Our analytic sample included 24 944 people diagnosed with any cancer. People with NAPD were less likely to receive treatment than people without psychosis (HR = 0.87, 95% CI = 0.82, 0.91). In addition, people with NAPD had a greater risk of death from any cause (HR = 1.68, 95% CI = 1.60, 1.76), compared to people without NAPD.
    Conclusions: The lower likelihood of receiving cancer treatment reflects disparities in accessing cancer care for people with psychotic disorders, which may partially explain the higher mortality risk following cancer diagnosis. Future research should explore mediating factors in this relationship to identify targets for reducing health disparities.
    Language English
    Publishing date 2024-03-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 439173-1
    ISSN 1745-1701 ; 0586-7614
    ISSN (online) 1745-1701
    ISSN 0586-7614
    DOI 10.1093/schbul/sbae013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Paraneoplastic Anti-Neuronal Nuclear Antibody Type 3 Neurologic Autoimmunity.

    Chandna, Nicholas / Budhram, Adrian / Blanchette, Phillip S / Climans, Seth A

    The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques

    2023  , Page(s) 1–3

    Language English
    Publishing date 2023-12-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 197622-9
    ISSN 0317-1671
    ISSN 0317-1671
    DOI 10.1017/cjn.2023.324
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Antibody-Drug Conjugates in Breast Cancer: Ascent to Destiny and Beyond-A 2023 Review.

    Xiao, Tian / Ali, Sanji / Mata, Danilo Giffoni M M / Lohmann, Ana Elisa / Blanchette, Phillip S

    Current oncology (Toronto, Ont.)

    2023  Volume 30, Issue 7, Page(s) 6447–6461

    Abstract: Antibody-drug conjugates (ADCs) are revolutionizing cancer treatment, adding another important new class of systemic therapy. ADCs are a specially designed class of therapeutics that target cells expressing specific cancer antigens using directed ... ...

    Abstract Antibody-drug conjugates (ADCs) are revolutionizing cancer treatment, adding another important new class of systemic therapy. ADCs are a specially designed class of therapeutics that target cells expressing specific cancer antigens using directed antibody-drug delivery and release a cytotoxic chemotherapeutic payload. Over the past two decades, improvements in ADC design, development, and research, particularly in breast cancer, have led to several recent landmark publications. These advances have significantly changed various treatment paradigms and revamped traditional classifications of breast cancer with the introduction of a potential new subtype: "HER2-low". This review will focus on several ADCs developed for breast cancer treatment, including trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG) and other newer emerging agents. It will provide an overview of the role of ADCs in breast cancer and discuss the opportunities and challenges they present. Additionally, our review will discuss future research directions to improve the selection of targets, combination therapies, and aim to improve drug safety. Important first-line metastatic and adjuvant clinical trials are underway, which may expand the role of ADC therapy in breast cancer. We foresee ADCs driving a new era of breast cancer treatment, adding to the steady incremental survival advantage observed in recent years.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/drug therapy ; Ado-Trastuzumab Emtansine/therapeutic use ; Immunoconjugates/therapeutic use
    Chemical Substances Ado-Trastuzumab Emtansine (SE2KH7T06F) ; Immunoconjugates
    Language English
    Publishing date 2023-07-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1236972-x
    ISSN 1718-7729 ; 1198-0052
    ISSN (online) 1718-7729
    ISSN 1198-0052
    DOI 10.3390/curroncol30070474
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cancer incidence and stage at diagnosis among people with psychotic disorders: Systematic review and meta-analysis.

    Wootten, Jared C / Wiener, Joshua C / Blanchette, Phillip S / Anderson, Kelly K

    Cancer epidemiology

    2022  Volume 80, Page(s) 102233

    Abstract: Research regarding the incidence of cancer among people with psychotic disorders relative to the general population is equivocal, although the evidence suggests that they have more advanced stage cancer at diagnosis. We conducted a systematic review and ... ...

    Abstract Research regarding the incidence of cancer among people with psychotic disorders relative to the general population is equivocal, although the evidence suggests that they have more advanced stage cancer at diagnosis. We conducted a systematic review and meta-analysis to examine the incidence and stage at diagnosis of cancer among people with, relative to those without, psychotic disorders. We searched the MEDLINE, EMBASE, PsycINFO, and CINAHL databases. Articles were included if they reported the incidence and/or stage at diagnosis of cancer in people with psychotic disorders. Random effects meta-analyses were used to determine risk of cancer and odds of advanced stage cancer at diagnosis in people with psychosis, relative to those without psychotic disorders. A total of 40 articles were included in the review, of which, 31 were included in the meta-analyses. The pooled age-adjusted risk ratio for all cancers in people with psychotic disorders was 1.08 (95% CI: 1.01-1.15), relative to those without psychotic disorders, with significant heterogeneity by cancer site. People with psychotic disorders had a higher incidence of breast, oesophageal, colorectal, testicular, uterine, and cervical cancer, and a lower incidence of skin, prostate, and thyroid cancer. People with psychotic disorders also had 22% higher (95% CI: 2-46%) odds of metastases at diagnosis, compared to those without psychotic disorders. Our systematic review found a significant difference in overall cancer incidence among people diagnosed with psychotic disorders and people with psychotic disorders were more likely to present with advanced stage cancer at diagnosis. This finding may reflect a need for improved access to and uptake of cancer screening for patients diagnosed with psychotic disorders.
    MeSH term(s) Humans ; Incidence ; Male ; Neoplasms/epidemiology ; Psychotic Disorders/epidemiology ; Risk
    Language English
    Publishing date 2022-08-08
    Publishing country Netherlands
    Document type Journal Article ; Meta-Analysis ; Review ; Systematic Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2508729-0
    ISSN 1877-783X ; 1877-7821
    ISSN (online) 1877-783X
    ISSN 1877-7821
    DOI 10.1016/j.canep.2022.102233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cancer incidence and stage at diagnosis among people with recent-onset psychotic disorders: A retrospective cohort study using health administrative data from Ontario, Canada.

    Wootten, Jared C / Richard, Lucie / Blanchette, Phillip S / Wiener, Joshua C / Anderson, Kelly K

    Psycho-oncology

    2022  Volume 31, Issue 9, Page(s) 1510–1518

    Abstract: Objective: Prior evidence on the relative risk of cancer among people with psychotic disorders is equivocal. The objective of this study was to compare incidence and stage at diagnosis of cancer for people with psychotic disorders relative to the ... ...

    Abstract Objective: Prior evidence on the relative risk of cancer among people with psychotic disorders is equivocal. The objective of this study was to compare incidence and stage at diagnosis of cancer for people with psychotic disorders relative to the general population.
    Method: We constructed a retrospective cohort of people with a first diagnosis of non-affective psychotic disorder and a comparison group from the general population using linked health administrative databases in Ontario, Canada. The cohort was followed for incident diagnoses of cancer over a 25-year period. We used Poisson and logistic regression models to compare cancer incidence and stage at diagnosis between people with psychotic disorders and the comparison group, adjusting for confounding factors.
    Results: People with psychotic disorders had an 8.6% higher incidence (IRR = 1.09, 95%CI = 1.05,1.12) of cancer overall relative to the comparison group, with effect modification by sex and substantial variation across cancer sites. People with psychotic disorders also had 23% greater odds (OR = 1.23, 95%CI = 1.13,1.34) of being diagnosed with more advanced stage cancer relative to the comparison group.
    Conclusions: We found evidence of elevated cancer incidence in people with non-affective psychotic disorders relative to the general population. The higher odds of more advanced stage cancer diagnoses in people with psychotic disorders represents an opportunity to improve patient participation in recommended cancer screening, as well as timely access to services for cancer diagnosis and treatment. Future research should examine confounding effects of lifestyle factors and antipsychotic medications on the risk of developing cancer among people with psychotic disorders.
    MeSH term(s) Cohort Studies ; Humans ; Incidence ; Neoplasms/epidemiology ; Ontario/epidemiology ; Psychotic Disorders/diagnosis ; Psychotic Disorders/epidemiology ; Psychotic Disorders/therapy ; Retrospective Studies
    Language English
    Publishing date 2022-07-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1118536-3
    ISSN 1099-1611 ; 1057-9249
    ISSN (online) 1099-1611
    ISSN 1057-9249
    DOI 10.1002/pon.5983
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  7. Article: Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer-A Literature Review.

    Giffoni de Mello Morais Mata, Danilo / Chehade, Rania / Hannouf, Malek B / Raphael, Jacques / Blanchette, Phillip / Al-Humiqani, Abdullah / Ray, Monali

    Cancers

    2023  Volume 15, Issue 17

    Abstract: Background: The overexpression of the human epidermal growth factor receptor 2 (HER2+) accounts for 15-20% of all breast cancer phenotypes. Even after the completion of the standard combination of chemotherapy and trastuzumab, relapse events occur in ... ...

    Abstract Background: The overexpression of the human epidermal growth factor receptor 2 (HER2+) accounts for 15-20% of all breast cancer phenotypes. Even after the completion of the standard combination of chemotherapy and trastuzumab, relapse events occur in approximately 15% of cases. The neoadjuvant approach has multiple benefits that include the potential to downgrade staging and convert previously unresectable tumors to operable tumors. In addition, achieving a pathologic complete response (pCR) following preoperative systemic treatment is prognostic of enhanced survival outcomes. Thus, optimal evaluation among the suitable strategies is crucial in deciding which patients should be selected for the neoadjuvant approach.
    Methods: A literature search was conducted in the Embase, Medline, and Cochrane electronic libraries.
    Conclusion: The evaluation of tumor and LN staging and, hence, stratifying BC recurrence risk are decisive factors in guiding clinicians to optimize treatment decisions between the neoadjuvant versus adjuvant approaches. For each individual case, it is important to consider the most likely postsurgical outcome, since, if the patient does not obtain pCR following neoadjuvant treatment, they are eligible for adjuvant T-DM1 in the case of residual disease. This review of HER2-positive female BC outlines suitable neoadjuvant and adjuvant systemic treatment strategies for guiding clinical decision making around the selection of an appropriate therapy.
    Language English
    Publishing date 2023-08-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15174336
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Early mortality in patients with cancer treated with immune checkpoint inhibitors in routine practice.

    Raphael, Jacques / Richard, Lucie / Lam, Melody / Blanchette, Phillip / Leighl, Natasha B / Rodrigues, George / Trudeau, Maureen / Krzyzanowska, Monika K

    Journal of the National Cancer Institute

    2023  Volume 115, Issue 8, Page(s) 949–961

    Abstract: Background: We sought to estimate the proportion of patients with cancer treated with immune checkpoint inhibitors (ICI) who die soon after starting ICI in the real world and examine factors associated with early mortality (EM).: Methods: We ... ...

    Abstract Background: We sought to estimate the proportion of patients with cancer treated with immune checkpoint inhibitors (ICI) who die soon after starting ICI in the real world and examine factors associated with early mortality (EM).
    Methods: We conducted a retrospective cohort study using linked health administrative data from Ontario, Canada. EM was defined as death from any cause within 60 days of ICI initiation. Patients with melanoma, lung, bladder, head and neck, or kidney cancer treated with ICI between 2012 and 2020 were included.
    Results: A total of 7126 patients treated with ICI were evaluated. Fifteen percent (1075 of 7126) died within 60 days of initiating ICI. The highest mortality was observed in patients with bladder and head and neck tumors (approximately 21% each). In multivariable analysis, previous hospital admission or emergency department visit, prior chemotherapy or radiation therapy, stage 4 disease at diagnosis, lower hemoglobin, higher white blood cell count, and higher symptom burden were associated with higher risk of EM. Conversely, patients with lung and kidney cancer (compared with melanoma), lower neutrophil to lymphocytes ratio, and with higher body mass index were less likely to die within 60 days post ICI initiation. In a sensitivity analysis, 30-day and 90-day mortality were 7% (519 of 7126) and 22% (1582 of 7126), respectively, with comparable clinical factors associated with EM identified.
    Conclusions: EM is common among patients treated with ICI in the real-world setting and is associated with several patient and tumor characteristics. Development of a validated tool to predict EM may facilitate better patient selection for treatment with ICI in routine practice.
    MeSH term(s) Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Retrospective Studies ; Carcinoma, Renal Cell ; Melanoma/drug therapy ; Kidney Neoplasms/drug therapy ; Ontario/epidemiology ; Lung Neoplasms/drug therapy
    Chemical Substances Immune Checkpoint Inhibitors
    Language English
    Publishing date 2023-05-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2992-0
    ISSN 1460-2105 ; 0027-8874 ; 0198-0157
    ISSN (online) 1460-2105
    ISSN 0027-8874 ; 0198-0157
    DOI 10.1093/jnci/djad090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The safety of seasonal influenza vaccination among adults prescribed immune checkpoint inhibitors: A self-controlled case series study using administrative data.

    Grima, Alicia A / Kwong, Jeffrey C / Richard, Lucie / Reid, Jennifer / Raphael, Jacques / Basta, Nicole E / Carignan, Alex / Top, Karina A / Brousseau, Nicholas / Blanchette, Phillip S / Sundaram, Maria E

    Vaccine

    2024  Volume 42, Issue 7, Page(s) 1498–1505

    Abstract: Background: Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of ... ...

    Abstract Background: Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of developing IRAEs among these patients given that vaccines are immunomodulatory. Previous vaccine safety studies on patients with cancer prescribed ICI therapy have demonstrated conflicting results.
    Methods: Using health administrative data from Ontario, Canada among adults diagnosed with cancer who had been prescribed ICI therapy and who had received an influenza vaccine from 2012 to 2019, we conducted a self-controlled case series study. The pre-vaccination control period started 42-days post-ICI initiation until 14-days prior to vaccination, the risk period was 1-42 days post-vaccination, and the post-vaccination control period was after the risk period until ICI discontinuation or a maximum period of two years. Emergency department (ED) visit(s) and/or hospitalization for any cause after ICI initiation was used to identify severe IRAEs. We fitted a fixed-effects Poisson regression model accounting for seasonality and calendar time to estimate relative incidence of IRAEs between risk and control periods.
    Results: We identified 1133 records of cancer patients who received influenza vaccination while prescribed ICI therapy. Most were aged ≥ 66 years (73 %), were male (63 %), had lung cancer (54 %), and had received ICI therapy with a programmed cell death protein 1(PD-1) inhibitor (91 %). A quarter (26 %) experienced an ED visit and/or hospitalization during the observation period. Rates of ED visits and/or hospitalizations in the risk vs. control periods were similar, with an incidence rate ratio of 1.04 (95 % CI: 0.75-1.45). Subgroup and sensitivity analyses yielded similar results.
    Conclusion: Seasonal influenza vaccination was not associated with an increased incidence of ED visit or hospitalization among adults with cancer treated with ICI therapy and our results support further evidence of vaccine safety.
    MeSH term(s) Adult ; Humans ; Male ; Female ; Immune Checkpoint Inhibitors/adverse effects ; Influenza, Human/prevention & control ; Influenza, Human/etiology ; Seasons ; Neoplasms ; Influenza Vaccines ; Lung Neoplasms ; Research Design ; Vaccination/adverse effects ; Ontario/epidemiology ; Retrospective Studies
    Chemical Substances Immune Checkpoint Inhibitors ; Influenza Vaccines
    Language English
    Publishing date 2024-02-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2024.01.023
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  10. Article ; Online: Utilization of Immunotherapy in Patients with Cancer Treated in Routine Care Settings: A Population-Based Study Using Health Administrative Data.

    Raphael, Jacques / Richard, Lucie / Lam, Melody / Blanchette, Phillip S / Leighl, Natasha B / Rodrigues, George / Trudeau, Maureen E / Krzyzanowska, Monika K

    The oncologist

    2022  Volume 27, Issue 8, Page(s) 675–684

    Abstract: Introduction: The introduction of immunotherapy (IO) in the treatment of patients with cancer has significantly improved clinical outcomes. Population level information on actual IO utilization is limited.: Methods: We conducted a retrospective ... ...

    Abstract Introduction: The introduction of immunotherapy (IO) in the treatment of patients with cancer has significantly improved clinical outcomes. Population level information on actual IO utilization is limited.
    Methods: We conducted a retrospective cohort study using provincial health administrative data from Ontario, Canada to: (1) assess the extent of IO use from 2011 (pre-IO funding) to 2019; and (2) identify factors associated with IO use in patients with advanced cancers for which IO is reimbursed including melanoma, bladder, lung, head and neck, and kidney tumors. The datasets were linked using a unique encoded identifier. A Fine and Gray regression model with death as a competing risk was used to identify factors associated with IO use.
    Results: Among 59 510 patients assessed, 8771 (14.7%) received IO between 2011 and 2019. Use of IO increased annually from 2011 (3.3%) to 2019 (39.2%) and was highest in melanoma (52%) and lowest in head and neck cancer (6.6%). In adjusted analysis, factors associated with lower IO use included older age (hazard ratio (HR) 0.91 (95% CI, 0.89-0.93)), female sex (HR 0.85 (95% CI, 0.81-0.89)), lower-income quintile, hospital admission (HR 0.78 (95% CI, 0.75-0.82)), high Charlson score and de novo stage 4 cancer. IO use was heterogeneous across cancer centers and regions.
    Conclusion: IO utilization for advanced cancers rose substantially since initial approval albeit use is associated with patient characteristics and system-level factors even in a universal healthcare setting. To optimize IO utilization in routine practice, survival estimates and potential inequity in access should be further investigated and addressed.
    MeSH term(s) Female ; Head and Neck Neoplasms ; Humans ; Immunologic Factors ; Immunotherapy ; Melanoma ; Ontario/epidemiology ; Retrospective Studies
    Chemical Substances Immunologic Factors
    Language English
    Publishing date 2022-03-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1409038-7
    ISSN 1549-490X ; 1083-7159
    ISSN (online) 1549-490X
    ISSN 1083-7159
    DOI 10.1093/oncolo/oyac085
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