Huseyin Mertsoylu

Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

PURPOSE/OBJECTIVES The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). METHODS AND MATERIALS A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. RESULTS Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. CONCLUSIONS In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.

Primary Renal Lymphoma: Report of Four Cases

Background: Although secondary renal involvement from systemic lymphoma is very frequent, primary renal lymphoma is a rare entity. It is characterized by aggressive histopathology, very early extra-renal infiltration and poor prognosis. Case Reports: Here, we report 4 cases of primary renal lymphoma presenting with unilateral renal masses, which after radiological and clinical examination were assumed to be renal cell carcinoma. 3 patients were diagnosed with Non-Hodgkin’s lymphoma by nephrectomy and one patient was diagnosed by open renal biopsy. Histopathological subtypes were diffuse large B cell lymphoma in 2 cases and non-Hodgkin’s lymphoma of small B cell type in the others. While 3 of the patients were treated with systemic chemotherapy, the fourth patient refused chemotherapy. 2 patients (no. 2 and 3) were still in complete remission and were followed regularly in the second and first year after diagnosis, respectively. Conclusions: Since it is difficult to diagnose primary renal lymphoma, most patients with this kind of tumor undergo radical nephrectomy, and diagnosis of primary renal lymphoma is delayed. The authors believe that both the delayed diagnosis due to anatomical difficulties and the histological aggressive characteristics of this disease are equally responsible for the poor outcome in the case of primary renal lymphoma.

Unilateral hand-foot syndrome: an extraordinary side effect of capecitabine.

Background: Hand–foot syndrome (HFS), the most common toxicity of capecitabine, is characterized by tingling, numbness, pain, erythema, dryness, rash, swelling, increased pigmentation, and/or pruritus of the palmar and/or plantar surfaces of the hands and/or feet. HFS is usually seen in both the hands and the feet, with varying severity. We have previously published a case report of dihydropyrimidine dehydrogenase (DPD) deficiency that manifested a variant of HFS. Case report: We report the case of a 65-year-old Turkish Cypriot male patient with advanced gastric cancer who developed pain, numbness, and reddening in his left palm and left sole 10 days after the fourth cycle of capecitabine at a dose of 1,000 mg/m2/day twice daily (BID) on days 1 to 14 every 21 days. On physical examination, he had unilaterally erythematous changes and skin scaling on his left sole and palm consistent with grade II HFS. After stopping administration of capecitabine and supportive management, the HFS resolved in a week’s time. Conclusions: To the best of our knowledge, this is the first case of capecitabine-induced unilateral HFS. Further investigation related to this toxicity associated with capecitabine is warranted.

Colon Adenocarcinoma and Solitary Tibia Metastasis: Rare Entity

IntroductionColorectal cancer is the third leading cause of cancer-related deaths in the world. Mostly, death occurs with complications of distant metastases.DiscussionEffective systemic chemotherapy regimen and resultant improved survival for patients are associated with an increased incidence of metastases at uncommon sites. Therefore, incidences of osseous metastases are rising at the last decade. Osseous metastases are mostly diffuse, along with visceral metastases.ConclusionMost common osseous metastatic sites are lumbal, sacral vertebrae, and pelvis region, probably because of colonic anatomical proximity to the paravertebral venous plexus. Herein, we report an uncommon case of isolated solitary tibia metastasis in the colorectal cancer patient and management of disease course.

Procalcitonin as a biomarker for infection-related mortality in cancer patients.

PURPOSE OF REVIEW Infectious diseases are the second leading cause of death following direct cancer-related complications in the field of oncology. Clinical studies using the classic inflammatory biomarkers, C-reactive protein, erythrocyte sedimentation rate, leukocytosis, and thrombocytosis fail to show a significant correlation between these biomarkers and infection-related mortality. It is therefore crucial to define new biomarkers that are not affected by the primary cancer and precisely show the severity of the infection to help in the decision-making process. RECENT FINDINGS A significant increase in the number of cancer patients in the past decades has created an exponential increase in the number of immunocompromised patients. Preemptive and typically unnecessary usage of broad-spectrum antibiotics is common during the treatment of these patients and may result in an increase in multidrug-resistant microbial strains. Recent clinical studies suggest that a significant reduction in antibiotic consumption may be achieved by procalcitonin-guided algorithms without sacrificing the outcome of patients with severe infection. SUMMARY In this article, we focus on procalcitonin and its potential role in differentiating cancer and infection-induced inflammation. Using this strategy may significantly reduce the usage of empirical broad-spectrum antibiotics and result in earlier discharge of patients.

Lack of Prognostic Significance of C-erbB-2 Expression in Low- and High- grade Astrocytomas

BACKGROUND Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. MATERIALS AND METHODS Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. RESULTS Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). CONCLUSIONS Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

Five-year follow-up results for patients diagnosed with anaplastic astrocytoma and effectiveness of concomitant therapy with temozolomide for recurrent anaplastic astrocytoma

Background: Anaplastic astrocytoma (AA; WHO grade-III) patients determination of prognostic factors helps generating multimodal therapy protocols. For this purpose, in the Baskent University, Adana Medical Research Center, specific characteristics of AA patients who have surgery were retrospectively investigated and factors which affect prognosis has been determined. Patients and Methods: Between January 2005 and 2009, 20 patients who have AA have been evaluated retrospectively. Totally, 20 patients had 31 operations. Sixteen patients had only adjuvant radiation therapy (RT). In the postoperative period, 8 patients received adjuvant RT. Nine of 10 patients with tumor recurrence received concomitant therapy with temozolomide (ConcT with TMZ) protocol. No adjuvant therapy protocol could be applied in three patients with poor general condition in the postoperative period. Results: Median survival for patients died was 16±17 months; one year survival was 75% and five year survival 25%. After univariate analysis, preoperative Karnofsky performance score (KPS) was ≥80 (P=0.005577*), postoperative KPS was ≥80 (P=0.003825*), type of tumor resection (P=0.001751*), multiple operations (P=0.006233*), and ConcT with TMZ protocol (P=0,005766*) were all positive prognostic factors which extend the survival. Conclusions: The results of the multivariate analysis did not put forward an independent prognostic factor acting on the survival period (P>0.05).

Little dose, huge toxicity: profound hematological toxicity of intrathecal methotrexate

A 60-year-old man presented with complaints of blurred vision and inability to raise the right eyelid 15 days after the last cycle of the planned six cycles R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone) for stage IV follicular lymphoma. Complete remission was confirmed after the fourth cycle by positron emission tomography. On physical examination, he had third and fourth cranial nerve palsies, whereas the remainder of the neurological examination was unremarkable. Magnetic resonance imaging of cranium and orbital region with gadolinium enhancement were normal. Upon detection of lymphocytic infiltration in the cerebrospinal fluid (CSF) by cytology, isolated leptomeningeal relapse of follicular lymphoma was diagnosed without any sign of systemic relapse. Treatment with intrathecal methotrexate 12.5 mg twice a week was planned. After the second dose of the intrathecal methotrexate, he developed a grade IV neutropenia, grade IV thrombocytopenia and grade IV oral mucositis. Intrathecal chemotherapy was then stopped. He also developed neutropenic fever and had to receive prolonged antibiotic administration. Intrathecal chemotherapy withmethotrexate, Ara-C, or both with or without hydrocortisone is considered the standard of care for prophylaxis and treatment of central nervous system (CNS) lymphoma [1]. Although, intrathecal methotrexate can cause some neurological complications [2,3], it is quite unusual to observe grade IV hematological toxicity. To the best of our knowledge, profound hematological toxicity has not been reported. Intrathecal methotrexate is not altered by metabolic processes in the CSF and it passes through the systemic circulation slowly via choroid plexus [4]. Its metabolism after intrathecal administration probably resembles the one in the presence of large volume of ascitis or pleural effusions where it is redistributed to the systemic circulation slowly. Even the small amounts at 10–15 mg of intrathecal methotrexate which pass to the systemic circulation can therefore cause the myelosuppression and other feared methotrexate complications. Bruce et al. [5] showed in pediatric patients that systemic methotrexate exposure can be greater after intrathecal than oral route. Our patient had none of the unfavorable factors that predispose for methotrexate toxicity such as renal insufficiency, third spacing of fluid in the body, anatomic abnormality of CSF flow or a history of using albumin bound drugs. In summary, one should be aware that intrathecal methotrexate administration may cause some unexpected toxicities. To our knowledge, this is the first case of profound hematological toxicity reported after intrathecal administration of methotrexate in the adult literature.

Concurrent Chemoradiotherapy with Vinorelbine plus Split-Dose Cisplatin may be an Option in Inoperable Stage III Non-Small Cell Lung Cancer: A Single-Center Experience

Background Concurrent chemoradiotherapy is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC). In this study we aimed to investigate the efficacy and toxicity of CCRT with split dose of cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) in patients with inoperable stage III NSCLC followed in our oncology clinic. Material/Methods Medical records of 97 patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with cisplatin-vinorelbine were retrospectively analyzed. Cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) were administered on days 1, 8, 22, and 29 during radiotherapy. Two cycles of consolidation chemotherapy were given. All patient data, including pathological, clinical, radiological, biochemical, and hematological data, were assessed retrospectively using our database system. Results Our study included 97 unresectable stage III NSCLC patients who were treated with CCRT. Median age was 58 years old (range 39–75) and 87 (89.7%) of the patients were men. ECOG performance score was 0–1 in 93 patients (95.9%). Squamous histology, the most common histology, was diagnosed in 46 patients (47.4%). Median follow-up time was 23.8 months. Median progression-free survival (PFS) and median overall survival time (OS) were 10.3 months and 17.8 months, respectively. Objective response rate and clinical benefit rate were 75.3% and 83.5%, respectively. Distant and local relapse rate were 57.1% and 42.9%, respectively. Hematological and non-hematological grade 3–4 toxicities were seen in 13 (13.4%) and 16 (16.5%) patients, respectively. Six (6.1%) patients died due to toxicity. Conclusions The results of this study suggest that split-dose cisplatin may offer fewer grade III–IV toxicities without sacrificing efficacy and could be an option in patients with inoperable stage III NSCLC during CCRT. Similar to past studies, despite high response rate during CCRT, distant relapse is the major parameter that influences patient survival in long-term in NSCLC.

Malignant pleural mesothelioma: a single-center experience in Turkey.

Background Malignant pleural mesothelioma is a rare lethal malignancy caused by asbestos exposure. It is more frequently seen in certain regions in Turkey. In this retrospective study, we aimed to analyse demographic, clinical, and pathological data and treatment-related features in 54 patients. Material/Methods The study included 54 patients diagnosed with malignant mesothelioma that were followed and treated. Results Of the 54 patients, 34 (55.6%) were male. The median age in men and women were 60.3 (38.2–77.2) and 65.8 (37.7–77.5) years, respectively. In 35 (64.8%), exposure to asbestosis was present. Epithelial type was found in 27 (50.0%), followed by mixed type in 7 (13.0%) patients, and in 20 (37.0%) patients the subtype could not be determined. The disease was staged as IV in 37 (68.5%) patients. In 28 patients (51.9%), it was right-sided and in 1 (1.9%) it was bilateral. The most frequent metastatic sites (in decreasing order) were lungs, mediastinum, diaphragm, liver, and thoracal wall. Of the 54 patients, 36 (66.6%) received 1st-line chemotherapy and 20 (37%) 2nd-line chemotherapy. Eighteen patients (33.3%) received radiotherapy; 11 (20.3%) with palliative intention and 7 (12.9%) with curative intention. Median overall survival (OS) was 12.03 months (95% CI 7.2–16.8). OS was not affected by sex (p=0.32), smoking history (p=0.51), alcohol consumption (p=0.36), family history (p=0.67), pleural effusion presence (p=0.80), operation (p=0.14), clinical stage (p=0.072), symptom at presentation (p=0.66), having mixed type histology (p=0.079), asbestos exposure (p=0.06), and type of 1st-line chemotherapy (p=0.161). On the contrary, it may be positively affected by good ECOG PS (0–1) (p<0.01), age below 65 (p=0.03), left-sided disease (p=0.01), receiving chemotherapy (p<0.01), having unilateral pleural effusion (p=0.018), and type of 2nd-line chemotherapy (p=0.025). Conclusions OS of our patients was better than that found in the literature, seeming to be positively affected by early stages, better ECOG PS, age below 65 years, left side involvement, and having second-line chemotherapy with cisplatin-gemcitabine or 3M. Overall treatment success seems to be comparable to what is currently expected.