Incidence of Disease Recurrence in Patients With Colon and Upper Rectum Adenocarcinoma Stage II and III Receiving Adjuvant Capecitabine Monotherapy: Do Number of Chemotherapy Cycles and Relative Dose Intensity of the Drug Play a Role?

INTRODUCTION/BACKGROUND: Adjuvant capecitabine monotherapy is an option for colon and upper rectum adenocarcinoma patients, providing they have stage II disease with an intermediate risk of recurrence, or stage III but they are above 70's or they have comorbidities. We wanted to examine whether the number of chemotherapy cycles and the relative dose intensity (RDI) of capecitabine monotherapy in the adjuvant setting are affecting disease recurrence. PATIENTS AND METHODS: We included patients with completely resected stage II and III colon and upper rectum cancer who received adjuvant capecitabine monotherapy, from 2003 until May 2020. Patients with early relapse, i.e. during chemotherapy or within 6 months after the completion of adjuvant chemotherapy, and those with rectal cancer who received radiotherapy were excluded. Patients were divided into 3 groups based on the number of chemotherapy cycles received and the RDI. Group A included patients with ≤4 cycles of chemotherapy, group B patients with >4 cycles of chemotherapy and RDI ≤80%, and group C patients with >4 cycles of chemotherapy and RDI >80%. Study's endpoint, was recurrence free survival (RFS). RESULTS: Two hundred twenty six patients with stage II and III disease (164 and 62 respectively) were included. Sixteen, 166 and 44 were included in groups A, B and C respectively. After a median follow-up of 41 months, 21 patients (9,3%) had relapsed. Patients belonging to group C were found to have a trend for lower relapse rate compared to patients belonging to group A or group B. CONCLUSION: Number of adjuvant capecitabine cycles and RDI might play a role in RFS in patients with stage II and III colon and upper rectum adenocarcinoma.

Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy-A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study.

Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients' tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm2 (DFS: HR = 0.58, p = 0.011 and HR = 0.65, p = 0.034 and OS: HR = 0.63, p = 0.043 and HR = 0.58, p = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC.

Potential Ophthalmological Side Effects Induced by Anti-Neoplastic Regimens for the Treatment of Genitourinary Cancers: A Review.

The outcomes of patients with genitourinary (GU) cancers have been steadily improving in recent years. Novel therapies have entered our armamentarium, while several other regimens are currently being studied in clinical trials. This recent explosion of new agents has improved patient survival and the quality of life for patients, but has also significantly increased the frequency of several side effects. The current review will focus on the potential ocular adverse reactions of GU neoplastic treatments. The broad spectrum of manifestations of ocular toxicity underscores the uniqueness and complexity of the anatomic, physiologic, and metabolic features of the human eye. Most side effects are mild in severity and transient, but some can be severe, disabling, and irreversible. Clinicians should be aware of complications that might be vision threatening and impact the patient's quality of life. In this review, we focused on the ocular toxicity of the antineoplastic regimens that are currently used for the treatment of GU, including prostate cancer, bladder cancer, renal cell carcinoma, testicular cancer, pheochromocytoma, adrenocortical carcinoma, and penile cancer.

The addition of the immunomodulator mifamurtide to adjuvant chemotherapy for early osteosarcoma: a retrospective analysis.

BACKGROUND: Current treatment recommendations for high grade non-metastatic osteosarcoma include perioperative chemotherapy and surgery. Despite this intensive protocol, approximately 40% of patients will relapse. The addition of the immunomodulator mifamurtide to adjuvant cytotoxic chemotherapy was associated with a significant improvement in 6-year overall survival (OS) in young patients with resectable osteosarcoma, leading to its approval in Europe and other countries. Very limited real-world data are reported on its use. METHODS: We retrospectively evaluated data from osteosarcoma patients who received mifamurtide in the adjuvant setting. Data were obtained from medical records in 2 high-volume bone sarcoma centers. The aim of this study was to collect real-world data on mifamurtide safety and efficacy in Greece. RESULTS: We identified 15 patients with completely resected osteosarcoma who received mifamurtide from September 2015 to January 2020. Median age at diagnosis was 24 years old (16-76). Osteosarcoma arose in the lower extremities (n = 12), in the upper extremities (n = 2) or in the ilium (n = 1). The majority of patients (n = 13) received cisplatin/doxorubicin/methotrexate as perioperative chemotherapy and the remaining patients cisplatin/doxorubicin. After a median follow-up of 46.9 months (range, 32.8-61.1), the median recurrence-free survival was 58.7 months (range, 18.5-98.8) and the median OS 64.1 months (range, 25.6-102.6). Except for fever and chills, the only adverse event probably related to mifamurtide was pericarditis (n = 1). CONCLUSIONS: Mifamurtide was well tolerated in a Greek osteosarcoma population, including patients older than 30 years. The small sample size and the non-comparative design do not allow drawing conclusions on the drug benefit in terms of survival.

Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC).

Background: We sought to compare patterns of response to immune checkpoint inhibitors (ICI) with respect to clinical and genomic features in a retrospective cohort of patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Methods: One hundred seventeen patients with R/M HNSCC treated with ICI were included in this study. Tumor growth kinetics (TGK) prior to and TGK upon immunotherapy (IO) was available for 49 patients. The TGK ratio (TGKR, the ratio of tumor growth velocity before and upon treatment) was calculated. Hyperprogression (HPD) was defined as TGKR ≥ 2. Results: HPD was documented in 18 patients (15.4% of the whole cohort). Patients with HPD had statistically significant shorter progression free survival (PFS) (median PFS 1.8 months (95% CI, 1.03-2.69) vs. 6.1 months for patients with non-HPD (95% CI, 4.78-7.47), p = 0.0001) and overall survival (OS) (median OS 6.53 months (95% CI, 0-13.39) vs. 15 months in patients with non HPD (95% CI, 7.1-22.8), p = 0.0018). In a multivariate Cox analysis, the presence of HPD remained an independent prognostic factor (p = 0.049). Primary site in the oral cavity and administration of ICI in the second/third setting were significant predictors of HPD in multivariate analysis (p = 0.028 and p = 0.012, respectively). Genomic profiling revealed that gene amplification was more common in HPD patients. EGFR gene amplification was only observed in HPD patients, but the number of events was inadequate for the analysis to reach statistical significance. The previously described MDM2 amplification was not identified. Conclusions: HPD was observed in 15.4 % of patients with R/M HNSCC treated with IO and was associated with worse PFS and OS. EGFR amplification was identified in patients with HPD.

Taxane & cyclophosphamide vs anthracycline & taxane-based chemotherapy as adjuvant treatment for breast cancer: a pooled analysis of randomized controlled trials by the Hellenic Academy of Oncology.

BACKGROUND: Adjuvant chemotherapy has an indisputable value for early breast cancer patients. Anthracycline and taxane-based regimens (TaxAC) have not been proven superior to taxane & cyclophosphamide (TC), a less toxic combination. Our objective was to estimate the cumulative evidence for non-inferiority of TC against TaxAC, in the adjuvant setting of patients with HER2-negative, breast cancer. RESULTS: Overall, 7,341 patients were included in this analysis. Superiority of TaxAC or non-inferiority of TC was not established either for the overall population (DFS HR, 1.11; 95% CI, 0.95-1.30; p = 0.18), or for the node-negative patients (HR, 1.05; 95% CI, 0.82-1.34; p = 0.71). A difference in DFS of 1.28% (TC DFS, 89.04%; 95% CI, 88%-90% & TaxAC DFS, 90.32%; 95% CI, 89%-91%) was found in favor of TaxAC. Lower risk of death was not established for either treatment regimen (OS-HR, 1.02; 95% CI, 0.82-1.25; p = 0.88). Overall, the toxicity profile favored TC. CONCLUSION: Although non-inferiority of TC was not proven, superiority of TaxAC is still questioned. The present analysis narrows the risk of recurrence between the treatment groups. Considering TC has a more favorable safety profile, the question as to which treatment regimen should be preferred under what circumstances, needs to be individualized according to patients' characteristics and desires. METHODS: Treatment efficacy data from The ABC trials, the Plan B trial and a trial by the Hellenic Oncology Research group (HORG) were pooled. Disease free survival (DFS) and overall survival (OS) were scrutinized. A HR of 1.18 for TC versus TaxAC was chosen to demonstrate inferiority.

Successful reversal of severe liver function impairment with Brentuximab vedotin in multiply relapsed/refractory classical Hodgkin lymphoma.

PURPOSE: To present our experience on the use of Brentuximab Vedotin (BV) in patients with relapsed/refractory classical Hodgkin Lymphoma (cHL) and severe liver function impairment with marked jaundice. METHODS: Two patients with relapsed/refractory cHL were evaluated. BV was administered in the presence of liver dysfunction and severe jaundice due to liver infiltration by cHL, as confirmed by PET-CT. Complete blood counts, biochemical profile, physical and imaging findings were reviewed to assess BV efficacy and tolerance. RESULTS: Case 1 had stage IVB, mixed cellularity cHL. Following ABVD chemotherapy, the patient experienced a relapse and responded to IGEV (ifosfamide, gemcitabine, vinorelbine, steroids) chemotherapy followed by autologous stem cell transplantation (ASCT). Thereafter, he experienced a second relapse with constitutional symptoms, severe jaundice and pancytopenia. Liver involvement was confirmed by PET-CT. Case 2 was admitted with a very late relapse of cHL. After a single cycle of gemcitabine-vinorelbine chemotherapy, which was not tolerated, the patient developed fever, anemia and jaundice, with laboratory findings indicating bone marrow and liver infiltration. The latter was confirmed by PET-CT. Both patients received BV monotherapy according to its formal indication at the reduced dose of 1.2 mg/kg due to severe liver impairment and experienced a rapid clinical and laboratory improvement. BV was well tolerated and offered a clinical benefit for approximately 4 months. CONCLUSIONS: BV was safely administered to patients with relapsed/refractory cHL and severe liver function impairment with marked jaundice due to liver involvement, offering significant clinical improvement and reversal of liver abnormalities. BV may serve as a bridge to further salvage combination chemotherapy or a transplant procedure.

Inflammatory Arthritis Induced by Pembrolizumab in a Patient With Head and Neck Squamous Cell Carcinoma.

Introduction: T cell checkpoint inhibitors targeting Programmed cell Death protein-1 (PD-1) have emerged as novel immunotherapy agents showing remarkable efficacy in head and neck squamous cell carcinoma (HNSCC). Despite important clinical benefits, they are associated with side effects that occur as a consequence of general immunological stimulation due to loss of T cell inhibition. Herein, we report the unusual case of inflammatory arthritis induced by anti-PD-1 agent pembrolizumab. Case report: A 55-years old male was treated with pembrolizumab at a dose of 200 mg every 3 weeks for a metastatic hypopharyngeal carcinoma. Following two cycles of immunotherapy, and while complete response of lung metastases was achieved, the patient presented with stiffness, swelling and pain of the right knee. Clinical examination and synovial fluid analysis revealed a seronegative inflammatory arthritis. Pembrolizumab therapy was interrupted and low-dose prednisone was administered with remarkable clinical improvement. Pembrolizumab was reintroduced, but after the fifth cycle, the patient developed inflammatory polyarthritis involving both knees and interphalangeal joints of both hands resulting in severe clinical deterioration. At that time, treatment with pembrolizumab was permanently discontinued. High-dose prednisone and methotrexate treatment led to remission of clinical symptoms. Conclusion: Pembrolizumab-induced inflammatory arthritis is an unusual rheumatic immune-related adverse event that physicians are likely to encounter as ICI use expands. Multidisciplinary management and rheumatology consultation are necessary to provide immediate treatment and avoid permanent joint damage.

Clinical Benefit of Pazopanib in a Patient with Metastatic Chondrosarcoma: A Case Report and Review of the Literature.

Chondrosarcoma is a rare malignancy characterized by the production of cartilage matrix, displaying heterogeneous histopathology and clinical behavior. Due to lack of effective treatment for advanced disease, the clinical management of metastatic chondrosarcoma is exceptionally challenging. Chondrosarcomas harbor molecular abnormalities, such as overexpression of platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta, which are required for cancer development, progression, and metastasis. Pazopanib is a potent and selective multitargeted tyrosine kinase inhibitor, which co-inhibits stem cell growth factor receptor (c-KIT), fibroblast growth factor receptor (FGFR), PDGFR, and vascular endothelial growth factor receptor (VEGFR) and has demonstrated clinical activity in patients with advanced previously treated soft tissue sarcoma. Herein, we describe the unique case of a patient with metastatic chondrosarcoma who derived clinical benefit from pazopanib after first-line chemotherapy failure.