Is there an association between lymph node size and hyperprogression in immunotherapy-treated patients?

BACKGROUND: Hyperprogressive disease (HPD) can be described as an accelerated increase in the growth rate of tumors combined with rapid clinical deterioration observed in a subset of cancer patients undergoing immunotherapy, specifically with immune checkpoint inhibitors (ICIs). The reported incidence of HPD ranges from 5.9% to 43.1% in patients receiving ICIs. In this context, identifying reliable predictive risk factors for HPD is crucial as it may allow for earlier intervention and ultimately improve patient outcomes. METHODS: This study retrospectively analyzed ten metastatic renal cell carcinoma (mRCC) patients. The identification of HPD was based on the diagnostic criteria proposed by Ferrara R et al. This study aimed to investigate whether there is an association between LN size and HPD using a cutoff value of 3 cm for LN size. Given the limited sample size, Fisher's exact test was used to test this association. We conducted a Kaplan-Meier (KM) analysis to estimate the median overall survival (OS) of patients with HPD and compared it to those without HPD. RESULTS: Three patients (30%) developed HPD, while seven (70%) did not. Fisher's exact test revealed a statistically significant association between the HPD and LN size ≥ 3 cm (p=0.008). In the HPD group, the median OS was significantly shorter, with a median OS of 3 months, whereas in the non-HPD group, the median OS was not reached (P =0.001). CONCLUSION: The present study found a significant association between LN size ≥ 3 cm in the pretreatment period and HPD development.

Prognostic Factors Influencing Survival in Stage II and Stage III Colorectal Cancer Patients.

Background Colorectal cancer (CRC) is a global health concern with rising incidence. This study analyzed demographic and clinicopathological factors influencing overall survival (OS) and disease-free survival (DFS) in Jordanian CRC patients. Methodology This retrospective, single-center study collected data from CRC patients at the Royal Medical Services, Jordan, from January 2018 to June 2020. Patient variables included disease stage, stage risk, tumor location, history of chemotherapy, and metastasis status. OS and DFS were defined as the time from surgery to death, last follow-up, or metastasis confirmation. Kaplan-Meier curves and Cox models were used for survival analysis. Results Of 127 CRC patients, 33.3% died during the follow-up period. Most patients were males (55.1%), diagnosed with stage III (55.9%), and classified as high risk (59.2%). Metastasis occurred in 24.4%, and 65.4% received chemotherapy. OS at one, two, and end of the follow-up years was 85.2%, 75.6%, and 66.9%, respectively. Metastasis-free rates were 85%, 78.5%, and 71%, respectively. Multivariate analysis showed that stage III (hazard ratio (HR) = 2.968) and high-risk stage (HR = 2.966) were associated with shorter OS and increased metastasis risk. Right-sided tumors (HR = 2.183) had shorter OS, while chemotherapy recipients (HR = 0.430) had longer OS. Stage III and high-risk stages were strong predictors of mortality, while only stage III and high-risk stages were robust predictors of metastasis. Demographic variables (sex and age) showed no significant associations with survival outcomes. Conclusions Our findings highlight the prognostic significance of disease stage, stage risk, tumor location, and chemotherapy in CRC survival among Jordanian patients. Understanding these factors can guide tailored treatment and improve outcomes.

The Impact of Palliative Chemotherapy on the Survival of Patients With Metastatic Colorectal Cancer in Jordan.

Background In Jordan, managing metastatic colorectal cancer (mCRC) is particularly complex, considering limited resources, access to advanced therapies, and unique patient demographics. Palliative chemotherapy, an approach aimed at relieving symptoms and improving the quality of life in patients with advanced cancer, including mCRC, has gained attention as a treatment strategy. While palliative chemotherapy may not aim for complete cancer eradication, it can extend survival, manage disease-related symptoms, and enhance the patient's overall well-being. However, deciding to pursue palliative chemotherapy for mCRC patients involves individual patient characteristics, performance status, disease aggressiveness, potential treatment-related adverse effects, and available healthcare resources. Given the need for region-specific insights into treatment outcomes, the proposed study seeks to investigate the impact of palliative chemotherapy on overall survival (OS), specifically within Jordan's healthcare landscape. Our study aims to showcase palliative chemotherapy's effectiveness on OS in first-line settings. Materials and methods This study is a retrospective analysis conducted at the Military Cancer Center (MCAC) in Jordan. It includes 73 patients diagnosed with mCRC between January 1, 2018, and January 1, 2020. Data were obtained from electronic medical records, and patients were monitored until June 10, 2023. Various patient characteristics were analyzed, including age, sex, primary tumor site, metastatic site, and treatment options for mCRC. The study evaluated the effectiveness of palliative chemotherapy in improving survival rates compared to BSC. Result We conducted a study with 73 participants, whose mean age was 60.37 ±13.5 years and a median of 63. Of these patients, 51 (69.9%) were male, and 22 (30.1%) were female. The primary site of the tumor was located on the left side in 32 patients (43.9%), on the right side in 26 patients (35.6%), and rectal cancer in 15 patients (20.5%). The most common site of the tumor was the sigmoid (17 patients, 23.3%). The liver was the most common site of metastasis (52 patients, 71.2%). Of the patients, 47 (64.4%) received palliative chemotherapy, while 26 (35.6%) were kept on best supportive care (BSC). Of those who received chemotherapy, FOLFIRI was administered to 32 patients (43.8%) and FOLFOX to 15 patients (20.5%). Based on the Kaplan-Meier curve, palliative chemotherapy patients had a significantly longer OS than those who only received BSC. Patients with palliative chemotherapy had a median OS of 12.4 months, while those who only had BSC survived for 5.3 months. The HR was 0.36 with a 95% confidence interval of 0.2-0.62, and the P-value was less than 0.001. Conclusion This study shows that palliative chemotherapy offers a notable advantage and a significant survival benefit compared to BSC.

Impact of KRAS Mutation on Survival Outcome of Patients With Metastatic Colorectal Cancer in Jordan.

Background Colorectal cancer (CRC) is the most prevalent cancer in males, with an incidence rate (IR) of 13.1%, and the second most prevalent cancer in females, with an IR of 8.4%, coming after breast cancer in Jordan. The present study was motivated by conflicting clinical data regarding the prognostic impact of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in patients with metastatic colorectal cancer (mCRC). Our study aimed to investigate if KRAS mutation conferred a negative prognostic value in Jordanian patients with mCRC. Materials and methods The current study is a retrospective study that collected data from a cohort of 135 mCRC patients diagnosed between 1 January 2017 and 1 January 2022 at our Oncology Department at the Jordanian Military Cancer Center (MCAC) using our patients' electronic medical records. The last follow-up date was 1 September 2022. From the cohort, we obtained data regarding age, sex, date of diagnosis, metastatic spread, KRAS status, either mutated KRAS or wild-type KRAS, and location of the primary tumor. All patients underwent tumor tissue biopsies to determine KRAS mutational status based on quantitative polymerase chain reaction and reverse hybridization from an accredited diagnostic laboratory at Jordan University Hospital. Statistical analysis was carried out to address the associations between KRAS mutation and the patients-tumor characteristics and their prognosis on survival. Results KRAS mutation was found in 40.3% of the participants in the study, and 56.7% had the wild type. There was a predilection of KRAS mutation, with 67% on the right side versus 33% on the left side (p = 0.018). Kaplan-Meier survival analysis showed worse survival outcomes in KRAS mutant patients (p = 0.002). The median overall survival in the KRAS mutant patients was 17 months (95% confidence interval (CI): 13.762-19.273) compared to 21 months (95% CI: 20.507-27.648) in patients with wild-type KRAS. Additionally, the Cox regression model identified that KRAS mutation carries a poorer prognosis on survival outcome hazard ratio (HR: 2.045, 95% CI: 1.291-3.237, p = 0.002). The test also showed statistical significance in the metastatic site (lung only). But this time, it was associated with a better survival outcome (HR: 0.383, 95% CI: 0.186-0.788, p = 0.009). Conclusion The present study shows that the presence of KRAS mutation has been found to negatively impact the prognosis and survival outcome of Jordanian patients with mCRC.

Delayed Hemolytic Transfusion Reaction With Hyperhemolysis Syndrome Due to Anti-M Alloantibody in Myelofibrosis: A Case Report.

Hyperhemolysis syndrome (HHS) and delayed hemolytic transfusion reaction (DHTR) commonly occur in patients with sickle cell disease (SCD) and thalassemia, due to the need for recurrent red blood cell (RBC) transfusion, but rarely in patients with myelofibrosis. HHS is a life-threatening condition that occurs with or without DHTR, in which both transfused and autologous RBCs are destroyed. It needs a high clinical suspicion for diagnosis, especially when there is a drop in hemoglobin level to the level of pretransfusion of RBCs, accompanied by hyperbilirubinemia and reticulocytopenia. The management of HHS includes avoiding RBC transfusion, supportive care, and immunomodulatory therapy. We present a case of HHS with DHTR in a patient with primary myelofibrosis who was treated successfully with steroids and splenectomy.

Hyperprogressive Disease In a Metastatic Renal Cell Carcinoma Patient After Receiving Immune Checkpoint Inhibitors: A Case Report.

Owing to their survival benefits, immune checkpoint inhibitors (ICIs) have emerged as the mainstay treatment for several types of malignant tumors including renal cell carcinoma (RCC). However, the usage of ICIs such as nivolumab, ipilimumab, and atezolizumab can be complicated by unexpected rapid clinical deterioration and acceleration of tumor growth. This adverse event is called hyperprogressive disease (HPD) with an incidence rate of 10-20%. Since its first description in 2016, efforts have been made to identify and predict this phenomenon. We report a case of a 34-year-old female patient diagnosed with metastatic renal cell carcinoma (mRCC) with sarcomatoid features. She underwent a left radical nephrectomy followed by combination ICIs (nivolumab/ipilimumab) therapy. However, she presented with a rapid clinical deterioration shortly after receiving her second cycle of ICIs. The radiological assessment showed new multiple bilateral lung nodules, new multiple mediastinal and left hilar lymph node involvement, and two focal areas of new appearance involving the left aspect of L3 lumbar vertebrae and left ischial bone. The diagnosis of HPD was made. Unfortunately, the patient died soon following her second infusion of the nivolumab/ipilimumab combination.