| 1. |
- Koliadi, Anthoula, 1978-
(författare)
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Cyclin A is an excellent proliferation marker for identifying luminal breast cancer subgroups using immunohistochemistry
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background. Gene arrays have demonstrated different outcomes for breast cancer subtypes highlighting the heterogeneity of breast cancer. The limited availability of gene expression analysis and financial issues have contributed to the development of surrogate markers to identify corresponding subgroups using IHC. 2011 ESMO and St Gallen guidelines suggest the use of an IHC panel consisting of ER, PgR, HER2 and Ki67 cut-off value ≥14 % (Ki6714%) for discriminating luminal A from B.The cut-off value suggested from 2013 St Gallens guidelines was ≥20% (Ki6720%). We wanted to evaluate if the different cut-off values for Ki67 or cyclins A/B1 could reliably separate luminal A from B. Patients. In a case-control study, we defined 190 women who died from breast cancer as cases and 190 women alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size ≤50 mm, no lymph node metastases and no adjuvant chemotherapy. Immunohistochemical evaluation of ER, PgR, HER2, Ki 67, cyclin A and cyclin B1 were utilized for subgrouping. Results. Conditional logistic regression analysis was used to estimate odds ratios (OR) for breast cancer death. Ki6714% did not detect differences in outcome between luminal A and B breast cancer (OR 1.4, 95% CI 0.8-2.26 p-value 0.24). Corresponding values for cyclin A was OR 3.6 (95% CI 1.8-7.0 p-value 0.00), cyclin B1 2.2 (95% CI 1.1-4.5 p-value 0.04) and Ki6720% 2.0 (95% CI 1.1-3.9 p-value 0.04) using luminal A as reference.Conclusion. In our study, Ki6714% failed to detect any difference in outcome between luminal A and B. In contrast, using cyclin A as a proliferation marker luminal B was found to have an almost 3.5 -fold higher risk of dying from breast cancer. Cyclin B1 and Ki6720%, could also separate luminal A from B but cyclin A separated more effectively these subtypes . We conclude that cyclin A distinctly separates luminal A from B in node negative breast cancer.
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| 2. |
- Koliadi, Anthoula, et al.
(författare)
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Cyclin B is an immunohistochemical proliferation marker which can predict for breast cancer death in low-risk node negative breast cancer
- 2010
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 49:6, s. 816-820
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Tidskriftsartikel (refereegranskat)abstract
- Patients with low-risk node negative breast cancer have an excellent prognosis with 5% breast cancer mortality at 10 years. However, prognostic factors are needed to identify poor prognostic patients who might benefit from adjuvant systemic therapy. Proliferation has been identified as the most important component of gene expression profiles. Cyclin B is a proliferative marker easily assessed by immunohistochemistry. We wanted to examine cyclin B as a prognostic factor in low-risk breast cancer patients. Patients and methods. Using an experimental study design, we compared women dying early from their breast cancer (n=17) with women free from relapse more than eight years after initial diagnosis (n=24). All women had stage I, node negative and hormone receptor positive disease. None had received adjuvant chemotherapy. Tumor samples were immunostained for cyclin B using commercial antibodies. Results. The mean percentage of cyclin B (12%) was significantly higher (p=0.001) in women dying from their breast cancer compared with women free from relapse ( 5%). High cyclin B (>= 9%) identified 11/17 patients dying from breast cancer and low cyclin B identified 22/24 patients free from relapse. The sensitivity and specificity of cyclin B was 65% and 92%, respectively. Discussion. We found that low-risk node negative patients with high expression of cylin B had a significantly worse outcome than patients with low expression of cyclin B. Cyclin B could separate patients with poor survival from those with good survival with 80% accuracy. We suggest that cyclin B might be a potent prognostic factor in this low-risk patient group.
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| 3. |
- Koliadi, Anthoula, 1978-
(författare)
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PPH3 is an independent prognostic factor in node negative breast cancer, however outperformed by cyclin A in the ER positive patients.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background. Proliferation conveys prognostic information and directs treatment choices in early and especially in estrogen receptor (ER) positive breast cancer. Ki67 is the proliferation marker, which is recommended by the 2013 St Gallen International Breast Cancer Conference to distinguish Luminal A-like from Luminal B-like breast cancer. However, the lack of standardization and absence of a clearly established cut-off value are limitations for the clinical use of Ki67. Recent studies in node negative breast cancer suggest that phosphorylated histone 3 (PPH3) may predict breast cancer death. Our aim was to examine the prognostic role of PPH3 compared to the proliferation markers Ki67, cyclin A and cyclin B1 in node negative breast cancer with a special focus on ER positive disease.Patients and methods. In a case-control study, we defined 190 women who died from node negative breast cancer as cases and 190 women who were alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size ≤50 mm, no lymph node metastases and no adjuvant chemotherapy. Of these 380 subjects, 249 had ER positive disease. Tumor tissues were immunostained for PPH3 using commercially available antibodies. The actual number of immunostained cells in 10 fields of view (PPH3 index) and the percentage of immunostained cells counting 200 and 500 tumor cells were calculated.Results. In node negative patients, PPH3 indexrevealed an odds ratio (OR) for breast cancer death of 2.6 (95% confidence interval (CI) 1.6-4.5 p-value <0.001). PPH3 was strongly correlated to Ki67, histological grade, mitotic count and cyclin A and B1. In ER positive patients the OR for PPH3 index was 2.9 (95% CI 1.6-5.2 p-value <0.001) while the OR for Cyclin A was 3.8 (95% CI 2.2-6.6 p-value <0.001), for cyclin B1 2.9 (95%CI 1.7-4.9 p-value <0.001) and for Ki67 1.6 (95% CI 0.9-4.9 p-value 0,09). However, multivariate analyses showed that cyclin A was the only independent prognostic marker for breast cancer death in ER positive patients, OR 3.6 (95% CI 1.6-8.1 p-value 0.002).Conclusion. In this study of node negative breast cancer patients, PPH3 showed to be a prognostic factor for breast cancer death. In ER positive patients PPH3 and cyclin A/B1 but not Ki67 could predict breast cancer death. However in the multivariate analysis of proliferation markers, only cyclin A remains as a prognostic factor.
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| 4. |
- Koliadi, Anthoula
(författare)
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The Prognostic Impact of Proliferation Markers in Breast Cancer with Emphasis on Cyclin B1 and PPH3
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to investigate the prognostic role of the proliferation markers cyclin B1 and Phosphorylated Histone 3 (PPH3) in breast cancer (BC).In paper I we used an experimental study design, we compared women dying early from their BC with women free from relapse more than eight years after initial diagnosis. All women had stage I, node-negative and hormone receptor positive disease. None had received adjuvant chemotherapy. We found that low-risk node negative patients with high expression of cyclin B1 had a significantly worse outcome than patients with low expression of cyclin B1.In paper II a population-based case control study was performed to further investigate the prognostic value of cyclin B1. One hundred and ninety women who died from BC were defined as cases and 190 women alive at the time for the corresponding case’s death were defined as controls. Inclusion criteria were tumor size 50 mm, no lymph node metastases, and no adjuvant chemotherapy. Two investigators evaluated the stainings independently. Cyclin B1 was found to be a prognostic factor for BC death that could identify high-risk patients with a good to very good reproducibility.Paper III aimed to investigate the role of proliferation in male breast cancer (MBC). One hundred and ninety-seven MBC tumors were stained for cyclin A, B1, D1 and Ki67. Overexpression of cyclin A and B1 and elevated mitotic count were predictive of breast cancer death. Ki67 was re-evaluated and different cut-offs were used, but no prognostic value could be demonstrated. On the other hand high levels of cyclin D1 were associated with better outcome in MBC.In paper IV we applied the immunohistochemichal panel suggested from international guidelines to the same patient material as in paper II, to discriminate luminal A from luminal B BC. We wanted to evaluate if different cut-off values of Ki67, cyclin A or B1 could more clearly separate luminal A from B. Cyclin A, B1 and Ki67 (cut-off 20%) could detect difference in outcome between these subtypes with cyclin A showing greater prognostic value.The aim of paper V was to examine the prognostic role of PPH3 compared to the proliferation markers Ki67, cyclin A and cyclin B1 with focus on ER positive disease. PPH3 was found to be a prognostic factor for breast cancer death but in the multivariate analysis including all proliferation markers, only cyclin A remained a prognostic factor.Finally, we conclude that both cyclin B1 and PPH3 are prognostic factors for breast cancer death, but are outperformed by cyclin A in ER positive patients. In male breast cancer prognostic factors need to be further studied.
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| 5. |
- Ladjevardi, Cecilia Olsson, et al.
(författare)
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Multiple immune-related adverse events secondary to checkpoint inhibitor therapy in patients with advanced cancer : association with treatment effectiveness
- 2024
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Checkpoint inhibitors (CPI) are widely used in cancer treatment with a potential of causing immune-related adverse events (IRAEs). Several studies have reported a positive correlation between development of IRAEs and improved survival outcome. However, few studies have focused on the potential role of multiple IRAEs on treatment effectiveness. This study aimed at investigating the association between multiple IRAEs and treatment effectiveness in terms of progression-free survival (PFS) and overall survival (OS) in advanced cancer patients.METHODS: We performed a retrospective cohort study at three Swedish centers. All patients (n=600) treated with PD-L1 or PD-1 inhibitor, in monotherapy or in combination for advanced cancer between January 2017 and December 2021 were included. Multiple IRAEs were defined as IRAEs involving more than one organ system either simultaneously or sequentially. Time-depending Cox-regression model to mitigate the risk for immortal time bias (ITB) was applied.RESULTS: The major tumor types were non-small cell lung cancer (205 patients; 34.2%) and malignant melanoma (196 patients; 32.7%). Of all patients,32.8% developed single IRAE and 16.2% multiple IRAEs. Patients with multiple IRAEs showed significantly improved PFS (Hazard Ratio, HR=0.78 95% Confidence Interval, CI: 0.57-0.98) and OS (HR=0.65 95% CI: 0.44-0.95) compared to patients with single IRAE or no IRAE (HR=0.46 95% CI:0.34-0.62 for PFS vs HR=0.41 95% CI: 0.28-0.60 for OS).CONCLUSION: In conclusion, our data supports a stronger association between development of multiple as opposed to single IRAEs and clinical effectiveness in advanced cancer patients treated with CPIs.
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| 6. |
- Ladjevardi, Cecilia Olsson, et al.
(författare)
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Predicting immune-related adverse events using a simplified frailty score in cancer patients treated with checkpoint inhibitors : A retrospective cohort study
- 2023
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:12, s. 13217-13224
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Checkpoint inhibitors (CPIs) are in widespread clinical use. Little is known about which patients are at risk for developing toxicity. It is essential being able to identify patients with higher risk of experiencing immune-related adverse events (IRAEs) before initiation of CPI treatment to optimize treatment decisions and follow-up strategy. The aim of this study was to investigate whether a simplified frailty score based on performance status (PS), age, and comorbidity expressed as Charlson comorbidity index (CCI) could predict development of IRAEs.METHODS: We performed a retrospective cohort study at three Swedish centers. All patients (n = 596) treated with PD-L1 or PD-1 inhibitor for advanced cancer between January 2017 and December 2021 were included.RESULTS: In total, 361 patients (60.6%) were classified as nonfrail and 235 (39.4%) as frail. The most common cancer type was non-small cell lung cancer (n = 203; 34.1%) followed by malignant melanoma (n = 195; 32.7%). Any grade of IRAE occurred in 138 (58.7%) frail and in 155 (42.9%) non-frail patients (OR: 1.58; 95% CI: 1.09-2.28). Age, CCI, and PS did not independently predict the occurrence of IRAEs. Multiple IRAEs occurred in 53 (22.6%) frail and in 45 (12.5%) nonfrail patients (OR: 1.62; 95% CI: 1.00-2.64).DISCUSSION: In conclusion, the simplified frailty score predicted all grade IRAEs and multiple IRAEs in multivariate analyses whereas age, CCI, or PS did not separately predict development of IRAEs suggesting that this easy-to-use score may be of value in clinical decision making but a large prospective study is needed to assess its true value.
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| 7. |
- Nilsson, Cecilia, et al.
(författare)
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High proliferation is associated with inferior Outcome in male breast cancer patients
- 2013
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Ingår i: Modern Pathology. - : Nature Publishing Group. - 0893-3952 .- 1530-0285. ; 26:1, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the lumina! subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide male breast cancer into molecular subgroups with different prognoses, the clinical importance of proliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to study proliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset of patients with high expression of cyclin A (hazard ratio (HR) 3.7; P=0.001) and B (HR 2.7; P=0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P=0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P=0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk for breast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation. Modern Pathology (2013) 26, 87-94; doi:10.1038/modpathol.2012.145; published online 24 August 2012
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| 8. |
- Niméus, Emma, et al.
(författare)
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Cyclin B1 is a prognostic proliferation marker with a high reproducibility in a population-based lymph node negative breast cancer cohort
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:4, s. 961-967
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Tidskriftsartikel (refereegranskat)abstract
- A large proportion of women with lymph node negative breast cancer treated with chemotherapy do not benefit from such treatment. Proliferation markers have been shown to recognize patients at high risk for recurrence. Ki67 has recently been included in the St Gallen guidelines. We investigated the prognostic importance of cyclin B1 in node negative breast cancer and included a study of reproducibility. In a population-based case-control study 190 women who died from breast cancer were defined as cases and 190 women alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size < 50 mm, no lymph node metastases, and no adjuvant chemotherapy. Tumor tissue was immunostained for cyclin B1. Two investigators evaluated the staining independently by counting approximately 100, 200, 500, and 1000 cells. Cyclin B1 was statistically significantly associated to breast cancer death, in both uni- and multivariate analyses (adjusted for tumor size, age, and endocrine therapy), with odds ratios 2-3 for both investigators. The agreement between the two investigators was good to very good, regardless of the number of counted cells (kappa values between 0.74 and 0.82).Cyclin B1 is a prognostic factor for breast cancer death in a population-based node negative patient cohort which can identify high-risk patients with a good to very good reproducibility. (c) 2009 UICC.
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| 9. |
- Rydén, Viktoria, et al.
(författare)
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The role of dacarbazine and temozolomide therapy after treatment with immune checkpoint inhibitors in malignant melanoma patients : A case series and meta-analysis
- 2024
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Ingår i: Pigment Cell & Melanoma Research. - : John Wiley & Sons. - 1755-148X. ; 37:3, s. 352-362
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Tidskriftsartikel (refereegranskat)abstract
- Dacarbazine (DTIC) and its oral counterpart temozolomide (TMZ) have been the most used agents in advanced malignant melanoma (MM) patients and they are still used routinely. The preferred first line treatment, immune checkpoint inhibitors (CPIs) might shape the tumor and the tumor microenvironment, possibly affecting the response to subsequent therapies. The aim of this study was to investigate the treatment effect of DTIC/TMZ in MM patients after CPI therapy in a consecutive patient cohort and through systematic literature review and meta-analysis. Thirty-five patients with advanced MM treated with DTIC/TMZ after previous CPI therapy in three Swedish regions between 2017 and 2021 were recognized and seven case series studies were identified through systematic database review. Pooled data from all 345 patients showed a median real-world progression-free survival (rwPFS) of 1.9 months and overall survival (OS) of 6.0 months. Three of these studies were included in a meta-analysis comparing DTIC/TMZ after CPI treatment, versus no previous immunotherapy, showing no statistically significant differences in rwPFS or OS but higher real-world response rate to chemotherapy for the prior-CPI treated group (Odds Ratio: 2.24; 95% Confidence Interval: 1.04-4.86). The current study supports consideration of DTIC/TMZ in later line of treatment in the immunotherapy era.
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| 10. |
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| 11. |
- Sköld, Camilla, 1981-
(författare)
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Impact of pregnancies on ovarian cancer : Risk, prognosis and tumor biology
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian cancer is the most lethal gynecological malignancy. The etiology is complex and not fully understood, partly since ovarian cancer is not one distinct disease, but rather several histologically and clinically different subtypes. The two main groups are epithelial (90%) and non-epithelial (10%) cancers, further divided into five epithelial and two main non-epithelial subtypes. Women who have given birth have a lower risk of developing epithelial ovarian cancer, and the risk is further reduced with each additional childbirth. However, the association between several pregnancy-related factors, such as pregnancy length, maternal age at birth, offspring size, and subsequent risk of ovarian cancer has been unclear. In addition, the impact of pregnancy-related risk factors on non-epithelial ovarian cancer is unknown. Further, the underlying mechanism behind the protection of childbirth has not been revealed and the prognostic impact of pregnancies is not established.In my first two studies, I evaluated associations between pregnancy-related factors and risk of epithelial ovarian cancer and its different subtypes [Study I] and non-epithelial ovarian cancer [Study II]. These case-control studies were based on linked data from the population-based medical birth registers and cancer registers in Denmark, Finland, Norway and Sweden. In Study I, preterm birth was associated with an increased risk of epithelial ovarian cancer among parous women, whereas increased number of births and pregnancies at older age were associated with decreased risk. In Study II, increasing age at last birth was associated with lower risk of sex cord-stroma cell tumors (SCSTs), as was shorter time since last birth.In Study III, the prognostic impact of parity on both epithelial and non-epithelial ovarian cancer by subtype was investigated by linkage of data from the Swedish medical birth register, the cancer register and the cause of death register. Parity was associated with reduced cancer-specific mortality in ovarian germ cell tumors. We found no prognostic impact of parity in patients with SCSTs or epithelial ovarian cancer.In Study IV, we investigated whether hormones and proteins involved in pregnancy and tumor development differed according to the woman’s parity status in patients with high-grade serous ovarian cancer. Parous women more often had progesterone receptor (PR) positive tumors, in comparison with nulliparous women, and increased number of children was associated with PR positive tumors.In summary, a woman’s reproductive history will not only impact on the risk of developing ovarian cancer, but also have a long-lasting influence on the tumor biology.
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| 12. |
- Sköld, Camilla, et al.
(författare)
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Parity is associated with better prognosis in ovarian germ cell tumors, but not in other ovarian cancer subtypes
- 2022
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 150:5, s. 773-781
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is influenced by reproductive factors, with a reduced risk of epithelial ovarian cancer in parous women. Nonepithelial ovarian cancer frequently affects young women and often precedes or occurs during the childbearing years. However, the impact of reproductive factors on ovarian cancer survival remains unclear: in epithelial ovarian cancer, data are conflicting, and subtype-specific associations have not been examined, and in nonepithelial ovarian cancer, it has not been studied. Using Swedish registers, we evaluated associations between women's reproductive history and cancer-specific mortality by subtype of epithelial and nonepithelial ovarian cancer in 3791 women born 1953 and later, diagnosed from 1990 to 2018. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using Cox-proportional hazard models. Parity was associated with a 78% decreased risk of cause-specific mortality in 243 women with germ cell tumors (GCTs) (parous vs nulliparous, adjusted for age at diagnosis: HR: 0.22 [95% CI 0.07-0.62]), with a decreased risk with increasing number of births (per birth: HR: 0.60 [95% CI 0.38-0.95]). We found no evidence of associations between parity and cause-specific mortality among the 334 patients with sex-cord stromal tumors, nor among the 3214 patients with epithelial ovarian cancer; neither overall, nor by subtype. In conclusion, in our large, population-based study, parity was associated with a clearly better prognosis in GCTs but not in the other ovarian cancer subtypes. Future research on how hormone exposure impacts GCT development may lead to a better understanding of mechanisms affecting survival.What's new?While risk of epithelial ovarian cancer is known to be influenced by pregnancy, the mechanisms underlying this association remain unclear. In this population-based study, the impact of reproductive history on ovarian cancer prognosis was evaluated by ovarian cancer subtype. Among women with germ cell tumors, parity was associated with 78 percent reduction in risk of cause-specific mortality. No associations were detected between parity and prognosis among women with sex-cord stromal tumors or epithelial ovarian cancer. These observations raise new questions about relationships between ovarian cancer prognosis and reproductive factors, including possible impacts of hormone exposure in pregnancy.
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| 13. |
- Tholander, Bengt, et al.
(författare)
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Complete response with combined BRAF and MEK inhibition in BRAF mutated advanced low-grade serous ovarian carcinoma.
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 125:4, s. 325-329
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Tidskriftsartikel (refereegranskat)abstract
- More effective treatments are needed for low-grade serous ovarian carcinoma (LGSOC). Our patient, who suffers from metastatic LGSOC, had received all established treatments. Sequencing analysis revealed an activating BRAF mutation. Therefore, combined treatment with BRAF and MEK inhibitors, which is the gold standard in malignant melanoma, was initiated. After eight months of therapy, the response was assessed as complete and the treatment is still, 3.5 years after initiation, of benefit. To our knowledge, no complete response on combined BRAF and MEK inhibitor treatment of low-grade serous ovarian cancer has previously been reported.
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| 14. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Improved survival without increased toxicity with influenza vaccination in cancer patients treated with checkpoint inhibitors
- 2021
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Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In international guidelines, influenza vaccination is recommended to cancer patients receiving antitumor treatment. Whether this recommendation should include patients treated with the recently introduced and now widely used checkpoint inhibitors (CPIs) is unclear. The immune hyperactivation after vaccination in a patient on CPI treatment may strengthen the antitumor immunity and improve patients´ prognosis. On the other hand, the hyperactivation might increase the risk for immune-related adverse events (IRAEs). Furthermore, there is a risk for decreased antitumor effect by the phenomenon of antigenic competition. Only results from few studies addressing survival have been reported and the results from studies on IRAEs are contradictory. We performed a multi-center retrospective cohort study at three Swedish centers in patients with metastatic cancer. All patients previously not treated with CPIs and who received monotherapy with a PD-1 or PD-L1 blocker between January 1st, 2016 until May 31st, 2019 were included. The most common type of malignancy was melanoma (47.8%) followed by non-small cell lung cancer (31.0%). Statistically significant longer PFS and OS were observed in multivariate analyses at 6-month landmark time in the vaccinated compared to the non-vaccinated group after adjustment for age, gender, comorbidity, performance status, CNS metastasis and line of treatment (p = .041 and 0.028, respectively). Furthermore, the incidence of any IRAE grade was comparable between vaccinated and non-vaccinated group (p = .85). In conclusion, the current study indicates that survival improves with influenza vaccination while not increasing the risk for side effects in cancer patients treated with checkpoint inhibitors. Hence, our results strongly support influenza vaccination in cancer patients receiving checkpoint inhibitors.
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