Advancing therapeutic frontiers in urothelial carcinoma: targeted strategies and clinical implications.

Urothelial carcinoma poses significant challenges in clinical management due to its aggressive nature and high prevalence. While most diagnoses involve localized disease, advanced urothelial carcinoma (aUC) often leads to short overall survival (OS). Historically, platinum-based chemotherapy has been the primary treatment for aUC, although its efficacy is limited.

Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer.

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies.

Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells.

Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy.

Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.

Purpose: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.

Methods: This is an investigator-initiated, multicenter, phase I trial.

Systemic Therapy for Advanced Hepatocellular Carcinoma: Current Stand and Perspectives.

Hepatocellular carcinoma often develops in the context of chronic liver disease. It is the sixth most frequently diagnosed cancer and the third most common cause of cancer-related mortality worldwide. Although the mainstay of therapy is surgical resection, most patients are not eligible because of liver dysfunction or tumor extent.

Cabozantinib plus Nivolumab Phase I Expansion Study in Patients with Metastatic Urothelial Carcinoma Refractory to Immune Checkpoint Inhibitor Therapy.

Purpose: This study investigated the efficacy and tolerability of cabozantinib plus nivolumab (CaboNivo) in patients with metastatic urothelial carcinoma (mUC) that progressed on checkpoint inhibition (CPI).

Patients And Methods: A phase I expansion cohort of patients with mUC who received prior CPI was treated with cabozantinib 40 mg/day and nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary goal was objective response rate (ORR) per RECIST v.

Systemic therapy issues: Immunotherapy in nonmetastatic urothelial cancer.

Non-muscle-invasive bladder cancer is one of the most common malignancies. Patients with intermediate-risk or high-risk disease can be treated with intravesical Bacillus Calmette-Guerin, a vaccine against tuberculosis. However, many of these patients will experience tumor recurrence, despite appropriate treatment.

Immunotherapy and Targeted Therapy for Hepatocellular Carcinoma: A Literature Review and Treatment Perspectives.

Advanced hepatocellular carcinoma is a prevalent and potentially aggressive disease. For more than a decade, treatment with sorafenib has been the only approved therapeutic approach. Moreover, no agent has been proven to prolong survival following the progression of disease after sorafenib treatment.

Systemic therapy in bladder preservation.

Bladder cancer is an aggressive and lethal disease. Even when presenting as localized muscle-invasive disease, the 5-year survival rate is about 70%, and the recurrence rate after radical cystectomy is approximately 50%. Neoadjuvant chemotherapy (NAC) has the potential to downstage the primary tumor and treat micrometastases, leading to a decrease in recurrence rates and an increase in cure rates.

Molecular Profiling of Exceptional Responders to Cancer Therapy.

Background: The vast majority of metastatic cancers cannot be cured. Palliative treatment may relieve disease symptoms by stopping or slowing cancer growth and may prolong patients' lives, but almost all patients will inevitably develop disease progression after initial response. However, for reasons that are not fully understood, a very few patients will have extraordinary durable responses to standard anticancer treatments.

Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors.

Purpose: We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances.

Patients And Methods: Patients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D).

Differences in Pathology and Mutation Status Among Colorectal Cancer Patients Younger Than, Older Than, and of Screening Age.

Background: Screening protocols for colorectal cancer are broadly recommended and effective in reducing mortality. However, populations from different age groups can harbor distinct pathologic and molecular profiles that can also be influenced by screening and polyp resection, especially in older ages.

Patients And Methods: We retrospectively analyzed tumors from stage IV colorectal cancer patients from a central pathology laboratory in Brazil that is a reference for mutational profiling countrywide.

Cooperation in a generalized age-structured spatial game.

The emergence and prevalence of cooperative behavior within a group of selfish individuals remains a puzzle for evolutionary game theory precisely because it conflicts directly with the central idea of natural selection. Accordingly, in recent years, the search for an understanding of how cooperation can be stimulated, even when it conflicts with individual interest, has intensified. We investigate the emergence of cooperation in an age-structured evolutionary spatial game.

Targeting the Hedgehog Pathway in Cancer: Current Evidence and Future Perspectives.

The Hedgehog pathway (HhP) plays an important role in normal embryonic development and its abnormal function has been linked to a variety of neoplasms. Recently, the complex mechanisms involved in this pathway have been deciphered and the cross talks with other important pathways involved in carcinogenesis have been characterized. This knowledge has led to the development of targeted therapies against key components of HhP, which culminated in the approval of vismodegib for the treatment of advanced basal cell carcinoma in 2012.

Clinical benefit and radiological response with BRAF inhibitor in a patient with recurrent ameloblastoma harboring V600E mutation.

Background: Ameloblastoma is a slow-growing neoplasm of the jaw, for which the standard treatment is surgical removal of the lesion with high recurrence rates and elevated morbidity. Systemic therapy is not established in the literature.

Case Presentation: We present a case of a 29-year-old woman diagnosed with an ameloblastoma of the left mandible who had been subjected to several surgical procedures over twenty years due to multiple local recurrences.

Second-Line Treatment for Advanced Pancreatic Adenocarcinoma: Is There a Role for Gemcitabine?

Purpose: Advanced pancreatic adenocarcinoma (PA) is an aggressive disease that has poor prognosis and frequently interferes with patient's quality of life. There has been progress in first-line regimens; however, there is no standard second-line regimen. The aim of this study is to analyze second-line gemcitabine after first-line fluorouracil (FU) + leucovorin (LV) + irinotecan + oxaliplatin (FOLFIRINOX) regimen.

Chemoradiotherapy versus chemotherapy as adjuvant treatment for localized gastric cancer: a propensity score-matched analysis.

Background: Treatment of localized gastric cancer (LGC) consists of surgical resection followed by adjuvant treatment. Both chemoradiation (CRT) and chemotherapy (CT) regimens have shown benefit in survival outcomes versus observation. However, there are few data comparing these approaches.

Next-generation Sequencing-based genomic profiling: Fostering innovation in cancer care?

Objectives: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer.

Methods: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis.

Combination of Irinotecan, Oxaliplatin and 5-Fluorouracil as a Rechallenge Regimen for Heavily Pretreated Metastatic Colorectal Cancer Patients.

Purpose: Our objective was to evaluate the benefit of re-exposing patients with refractory metastatic colorectal cancer (mCRC) to a combination of oxaliplatin, irinotecan and 5-fluorouracil treatment.

Methods: We retrospectively analysed patients with mCRC who received a combination of oxaliplatin, irinotecan and fluorouracil as a rechallenge regimen after progressing on the same drugs. Both FOLFOXIRI and FOLFIRINOX were used.

Unraveling molecular pathways of poorly differentiated neuroendocrine carcinomas of the gastroenteropancreatic system: A systematic review.

Background: Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive tumors. Their molecular pathogenesis is still largely unknown, and consequently, the best therapeutic management also remains to be determined. We conducted a systematic review on molecular alterations found in gastroenteropancreatic NECs (GEP-NECs) and discuss potential applications of targeted therapies in setting.

Acquired hemophilia A in a patient with advanced prostate cancer.

Acquired hemophilia A (AHA) is a rare disorder that results from the presence of autoantibodies against the clotting factor VIII (FVIII) causing hemorrhagic disorders. This entity is mostly associated with autoimmune diseases, pregnancy, the postpartum period, drugs and malignancy. Among the solid cancers, prostate neoplasm is the most common cause of AHA.

Plasmacytoid urothelial carcinoma: a case of histological variant of urinary bladder cancer with aggressive behavior.

Plasmocytoid variant urothelial carcinoma (PVUC) of the urinary bladder is a rare histological variant of transitional cell carcinoma. Data regarding PVUC shows that this neoplasia presents a distinctive clinical outcome represented by aggressive behavior and poor survival rate. The authors report a case of a 57-year-old male patient with a 3-month history of hematuria and pelvic pain.