Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group.

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.

Leukocytoclastic vasculitis associated with capecitabine.

BACKGROUND: Leukocytoclastic vasculitis (LCV) is a vasculitic inflammation against blood vessels. Various anticancer therapies can cause vasculitis, but capecitabine-induced LCV is an unusual entity. Here, we describe an LCV case associated with neoadjuvant capecitabine use for locally advanced rectal cancer (LARC). CASE REPORT: A 70-year-old man presented with rectal bleeding. A colonoscopic biopsy revealed rectal adenocarcinoma and he was diagnosed with LARC after imaging studies. Capecitabine plus radiation therapy was started as a neoadjuvant treatment. MANAGEMENT AND OUTCOME: Seven days after the first capecitabine dose, the patient was admitted with a rash. The LCV diagnosis was histopathologically proven. Capecitabine was withheld. After the patient's rash began to regress under corticosteroid pressure, capecitabine was started at a lower dose. His treatment was completed successfully with oral corticosteroids plus low-dose capecitabine. DISCUSSION: We aimed to point out a rare and unusual adverse effect of a frequently used drug in oncologic practice.

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study.

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice.  Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

The effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

Continuous angiogenesis inhibition in the treatment for von Hippel-Lindau-related hemangioblastomas of retina and spinal cord.

Hemangioblastomas of central nervous system are rare and indolent. Twenty-five percent of cases are in association with von Hippel-Lindau disease. Surgery is the standard therapy but un-resectable or recurrent cases need radiation or systemic therapy. Defective von Hippel-Lindau tumor suppressor gene leads to vascular endothelial growth factor overexpression and enhance angiogenesis. Here we report a 19-year-old male, diagnosed at pediatric age, who had retinal and spinal cord hemangioblastomas. He was treated 34 months with bevacizumab, afterwards 12 months with thalidomide and tertiary therapy with pazopanib for 9 months which still goes on. In case of need, radiation and surgical procedures were performed. Vascular endothelial growth factor inhibition continuity is a good therapeutic option, which improves outcomes of von Hippel-Lindau-related hemangioblastomas.

Hypercalcemia associated with squamous cell carcinoma of renal pelvis: A case and review of the literature.

Renal pelvis squamous cell carcinoma (RSCC) is a rare tumor. It starts with nonspecific symptoms and it is usually at an advanced stage with a poor prognosis at the time of diagnosis. SCC-associated hypercalcemia is a well-known paraneoplastic syndrome; however RSCC-associated hypercalcemia is a rare condition. Our patient is a 57-year-old-male patient with no bone metastases. Based on the literature screening on PubMed Database for paraneoplastic malignant hypercalcemia-associated RSCC, we found a few cases.

The importance of stromal and intratumoral tumor lymphocyte infiltration for pathologic complete response in patients with locally advanced breast cancer.

OBJECTIVE: Increased tumor-infiltrating lymphocytes (TILs) in breast carcinoma tissues is an independent predictive factor for pathologic complete response (pCR). The increased intratumoral and stromal TILs (sTILs) in breast cancer (BC) have significant prognostic effects. In this study, we evaluated whether pCR rates to neoadjuvant chemotherapy (NACT) are higher in tumors with increased number of TILs in the pretreatment biopsy. MATERIALS AND METHODS: We retrospectively evaluated the number of TILs in intratumoral TILs (iTILs) and sTILs compartments from pretreatment full-face hematoxylin and eosin-stained sections of 62 patients with locally advanced BC (LABC) who received NACT. The capacity of sTILs and iTILs in predicting pCR to NACT in LABC analyzed using receiver operating characteristic (ROC) curve analysis. RESULTS: According to ROC curve analysis, the optimum sTILs and iTILs cut-off points (the number of positive cells per square millimeter of tissue) for patients with LABC patients with pCR (+) were 19 (area under the curve (AUC): 0.668, 95% confidence interval [CI] [0.501-0.835],P = 0.064) and 4 (AUC: 0.786, 95%CI [0.666-0.907],P = 0.002), respectively. Of the 62 patients, 26 had sTILs >19 and 25 had iTILs >4. The patients were divided into two according to percent of sTILs (sTILs >19 and sTILs ≤19 groups) and iTILs (iTILs >4 and iTILs ≤4 groups). Both sTILs >19 and iTILs >4 patients were associated with development higher pCR. While pCR was significantly higher in iTILs >4 patients (P = 0.002), it was not significantly in sTILs >19 patients (P = 0.107). CONCLUSIONS: There is significantly an association between pCR and increased number of intratumoral TILs (>4 cells/mm 2 of tissue) in BC who received NACT.

Multiple pelvic cysts in a patient with familial Mediterranean fever: Benign cystic mesothelioma.

Benign cystic mesothelioma (BCM) is a rare tumor arising from endothelial cells of the pelvic visceral or parietal peritoneum. It is a clinically and histopathologically benign disease. Etiology and pathogenesis of BCM remain unclear. Familial Mediterranean fever (FMF) is an inherited disorder characterized by episodes of fever, and abdominal, chest and/or joint inflammation. Association between malignant mesothelioma and FMF has been reported previously; however, co-existence of FMF and BCM is rare. Here, we report a case of BCM in a 43-year-old male patient with FMF.

Docetaxel plus cisplatin plus fluorouracil versus carboplatin plus fluorouracil-cetuximab in first-line setting in patients with recurrent or metastatic head and neck squamous cell cancer who did not previously receive neoadjuvant or adjuvant chemotherapy, which is standard?

BACKGROUND: The prognosis of recurrent or metastatic head and neck squamous cell cancer (HNSCC) is very poor. In the present retrospective study, we compared the impact of docetaxel plus cisplatin plus fluorouracil (TCF), and cisplatin plus fluorouracil plus cetuximab (CF-Ctx) regimens on the prognosis of patients with recurrent or metastatic HNSCC in first-line. MATERIALS AND METHODS: A total of 70 patients were evaluated as two groups, according to treatment protocol: TCF (n: 47) and CF-Ctx (n: 23). The groups were compared regarding survival. RESULTS: The median progression-free survival was 7.3 and 8.3 months, TCF and CF-Ctx groups, respectively, (P = 0.280). The median overall survival (OS) was 15.6 and 9.3 months for TCF and CF-Ctx groups, respectively, (P = 0.029). The dose reduction and using of granulocyte colony stimulating factor were significantly higher in TCF group (P = 0.048 and P = 0.018, respectively). CONCLUSION: In first-line setting, TCF regimen is superior to CF-Ctx regimen in terms of OS in patients with recurrent or metastatic HNSCC, who did not previously receive neoadjuvant or adjuvant chemotherapy.

Mean Platelet Volume as an Independent Predictive Marker for Pathologic Complete Response after Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer.

BACKGROUND: The impact of mean platelet volume (MPV) on prognosis, diagnosis and response to therapy in cancer patients has been widely investigated. In the present study, we evaluated whether MPV at diagnosis has predictive value for pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC). MATERIALS AND METHODS: A total of 109 patients with LABC from Akdeniz University and Antalya Research and Training Hospital were evaluated retrospectively. RESULTS: ROC curve analysis suggested that the optimum MPV cut-off point for LABC patients with pCR (+) was 8.15 (AUC:0.378, 95%CI [0.256- 0.499], p=0.077). The patients with MPV <8.15 had higher pCR rates (29.2% vs. 13.1%, p=0.038). After binary logistic regression analysis, MPV and estrogen receptor absence were independent predictors for pCR. CONCLUSIONS: MPV has an independent predictive value for pCR after neoadjuvant chemotherapy in patients with LABC.

The Neutrophil to Lymphocyte Ratio is an Independent Prognostic Factor in Patients with Metastatic Gastric Cancer.

Inflammation can play an important role in cancer progression and the prognostic importance of neutrophil to lymphocyte ratio (NLR), a marker of inflammation, in cancer is a current investigation topic. In the present study, we aimed to determine whether there is a prognostic link between NLR and metastatic gastric cancer (mGC). A total of 143 patients from the Akdeniz University and Antalya Training and Research Hospital database were retrospectively analyzed. The median NLR value was 3.34. The median overall survival (OS) and median progression-free survival (PFS) were 11.6 and 7.9 months, respectively, in patients with NLR<3.34 while these values were 8.3 and 6.2 months respectively in patients with NLR >3.34 (p<0.001 and p=0.011, respectively). Our study showed that increased NLR is an independent prognostic factor associated with short survival in patients with mGC.

Fatal posterior revesible leukoencephalopathy syndrome associated coma induced by bevacizumab in metastatic colorectal cancer and review of literature.

Posterior reversible leukoencephalopathy syndrome (PRES) is a syndrome characterized by headache, hypertension, confusion, visual disturbance, and seizures accompanied by subcortical vasogenic edema, predominantly involving the parietal and occipital lobes. The syndrome is usually described in malignant hypertension, eclampsia, renal failure, immunosuppressive, and cytotoxic chemotherapies. Bevacizumab, a monoclonal antibody that binds to the vascular endothelial growth factor (VEGF) has been linked to PRES. We carried out review of reports documenting the occurrence of PRES in patients receiving bevacizumab. This literature review was conducted by utilizing PubMed Database. If early diagnosed, PRES is reversible. We present a case of fatal PRES-associated coma induced by bevacizumab in metastatic colorectal cancer.

Ipilimumab may increase the severity of cutenaous toxicity related to radiotherapy.

Ipilimumab, monoclonal antibody against cytotoxic T-lymphocyte antigen-4 and, radiotherapy are commonly used to treat unresectable and metastatic melanoma. As a result of upregulation of immune system with ipilimumab, many immune-related adverse effects, such as dermatitis, colitis, hepatitis, and hypophysitis, have been previously reported in literature. Typically, these effects are treated with high-dose steroids and mostly heal up. Here, we report a case who was receiving radiotherapy due to metastatic malignant melanoma with atypical generalized rash, which was enlarged with concurrent ipilimumab treatment.

Neutrophil to lymphocyte ratio is an independent prognostic factor in patients with recurrent or metastatic head and neck squamous cell cancer.

The neutrophil to lymphocyte ratio (NLR) has been widely investigated for its prognostic significance in cancer. In the present study, we aimed to determine whether NLR is a prognostic factor in patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC). A total of 79 patients from the Akdeniz University database were retrospectively analyzed. The cut-off NLR was set at 2.93; patients with NLR >2.93 had a median overall survival (OS) of 12.1 months, whereas the median OS was not reached for patients with NLR ≤2.93 (P=0.027). On multivariate analysis, NLR and recurrence or metastatic site were found to be independent prognostic factors for OS (P=0.014 and P=0.002, respectively). Therefore, NLR was identified as an independent prognostic factor for OS in patients with recurrent or metastatic HNSCC.

T-cell prolymphocytic leukemia presenting with leukemic serous effusion in a prostate cancer patient.

T-cell prolymphocytic leukemia (T-PLL) is highly aggressive mature postthymic lymphoproliferative disorder, which is characterized by several clinical features. Leukemic prolymphocytes are found in the peripheral blood, bone marrow, lymph nodes, spleen, liver, and sometimes skin. T-PLL and solid tumor coincidence was reported by only four previous cases. Solid tumor components included breast cancer, classic Kaposi sarcoma, gastric cancer, and lung cancer in those cases. We report the first case of T-PLL, an extremely rare disease, presented with serous effusion in an elderly prostate cancer patient in literature.

Experience of bevacizumab in a patient with colorectal cancer after renal transplantation.

Bevacizumab is a drug that is widely used for the first-line treatment of metastatic colorectal cancer (mCRC). Bevacizumab neutralizes vascular endothelial growth factor and can lead to proteinuria and renal damage. In this case, experience on full dose short-time treatment of bevacizumab in a patient under immunosuppressive treatment for renal transplantation with chronic renal failure has been shared. The patients were diagnosed with mCRC 7 months ago. The patient had multiple liver metastases at the time of the diagnosis. He had a history of renal transplantation 2 years ago because of renal failure, and he had been under immunosuppressive treatment for this reason. 5-fluorouracil-leucovorin-irinotecan -bevacizumab regimen was begun for the treatment of mCRC. The dose of bevacizumab was 5 mg/kg/day for 14 days. There was 2.5 g/day of proteinuria at the start of the treatment. However, renal dysfunction progressed, and proteinuria increased to 4 g/day in the 3rd month of treatment. In this case, the experience of using bevacizumab in a patient under immunosuppressive treatment for renal transplantation with chronic failure has been presented.

Gastrointestinal stromal tumor and isolated anterior tibial muscle metastasis as first recurrence.

In the presented case, we report gastrointestinal stromal tumor (GIST) in a patient using adjuvant imatinib in whom isolated metastasis to anterior tibial muscle as first recurrence was diagnosed. A 66-year-old woman was diagnosed with GIST on October 2012 and was followed up with adjuvant imatinib until June 2014. In this time, there was a nodular and fixed lesion with 1.5-2 cm of diameter in right lateral pre-tibial area. The lesion was resected, and it was reported as GIST metastasis by pathologist. GIST metastasis to muscle under knee is a generally unexpected area for any tumor metastasis. In modern treatment era, due to the increasing survival of the patients with GIST using targeted therapy, the metastatic pattern and behavior of GIST may be changing.

Molecular types and neoadjuvant chemotherapy in patients with breast cancer- while molecular shifting is more common in luminal a tumors, the pathologic complete response is most frequently observed in her-2 like tumors.

BACKGROUND: Pathologic complete response (pCR) is one of the most important target end-points of neoadjuvant chemotherapy (NACT) in patients with breast cancer (BC). In present study, we aimed to investigate the relationship between molecular subtypes and NACT in patients with BC. MATERIALS AND METHODS: Using the Akdeniz University database, 106 patients who received NACT for operable breast cancer were retrospectively identified. Prognostic factors before and after NACT were assessed. According to the molecular subtypes, molecular shifting after NACT and tumoral and nodal response to NACT were analyzed. RESULTS: The distribution of subtypes was: Luminal A, 28.3% (n=30); Luminal B, 31.1% (n=33); HER2-like, 24.5% (n=26); and basal like/ triple negative (BL/TN), 16.0% (n=17). According to molecular subtypes, pCR rates in both breast and axillary were 0%, 21.4%, 36.4% and 27.3% for luminal A, luminal B, HER2-like and BL/TN, respectively (p=0.018). Molecular subtype shifting was mostly seen in luminal A type (28.6%) after the NACT. The pCR rate in breast and axillary was significantly higher in patients with HER2-like type BC. CONCLUSIONS: In patients with HER-2 like type BC, NACT may be offered in early stages. Additionally, due to molecular shifting, adjuvant treatment schedule should be reviewed again, especially in the luminal A group.