Ali Ayberk Besen

A case report of bevacizumab-related osteonecrosis of the jaw: Old problem, new culprit

Osteonecrosis of the jaw (ONJ) is well-characterized syndrome predominantly reported in advanced stage cancer patients who had used long term bisphosphonates to treat bone metastases. Rarely, ONJ has been reported in patients who have not used bisphosphonates. Here we present an extremely rare occurrence of ONJ that occurred in a patient who received bevacizumab containing chemotherapy without bisphosphonate therapy. A 51-year-old male with history of metastatic carcinoma of the sigmoid colon was diagnosed in December 2010. He was subsequently treated with palliative chemotherapy with infusional fluorouracil, leucovorin, oxaliplatin, and bevacizumab for six cycles. Bevacizumab was initiated at a dose of 5 mg/kg on a 2-week schedule. Two weeks following the last dose of chemotherapy, the patient presented with a 2-week history of lower jaw pain, ulcer in the mouth, and difficulty chewing. He denied any recent history of dental surgery or radiation therapy at affected site. A detailed dental examination revealed a small area of bone exposure and ulcer in the right posterior mandible, measuring approximately 3 3 mm in diameter. The surrounding soft tissue appeared ulcerated and necrotic, with no evidence of infection. Pantomography and axial computerized tomography revealed a minor cortical sclerotic bone lesion (Fig. 1A and B). There was no evidence of fistulae or abcesses. After curettage and primary restoration of the necrotic lesion, pathological findings consistent with osteonecrosis and actinomyces superinfection were noted (Fig. 2). The suspected diagnosis of jaw osteonecrosis was confirmed. It was suggested that the patient’s symptoms were likely related to his use of bevacizumab, even though there was not a period of antecedent bisphosphonate use. Actinomycosis causing infection in this case, we believe that just an incidental findings rather than a causal role. ONJ is defined by the presence and persistence of exposed bone in the jaw over a period of 6–8 weeks. Nitrogen-containing intravenous BP treatment has been implicated in 94% of ONJ cases. Development of ONJ can occur spontaneously or can be facilitated by tooth extraction, dental procedures, poor oral hygiene, and actinomyces infections. The pathogenesis of bisphosphonate-related ONJ is believed to involve inhibition of angiogenesis and bone formation. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and bone formation. Bevacizumab (Bev), a VEGF inhibitor, has been shown to effectively treat a variety of malignancies when combined with chemotherapy. Bev has been associated with severe adverse events such as thromboembolic episodes, hypertension hemorrhage, and gastrointestinal perforation. Among Bev users, devleopment of ONJ is very rare, only having been recently reported in a small number of cases. Thus, this case study is important in the understanding

Promising efficacy of sorafenib in a relapsed thymic carcinoma with C-KIT exon 11 deletion mutation

Advanced thymic carcinoma (TC) is a very aggressive disease. To date there are no established treatment options for the refractory and recurrent disease and only a few prospective trials have been conducted in patients with TC. Here we present a case of a relapsed TC patient, who, by using combination chemotherapy, showed a positive response to sorafenib with C-KIT exon 11 mutation.

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.

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.

Association of vitiligo and response in patients with metastatic malignant melanoma on temozolomide

Vitiligo-like lesions, although rare, are believed to be a prognostic factor in malignant melanoma. While a predictive role for such lesions was shown with immunomodulatory therapies, this relation was not demonstrated with temozolomide. We present 3 patients with metastatic malignant melanoma who developed vitiligo-like skin lesions accompanying good response to treatment and prolonged survival. Onset of vitiligo-like lesions with temozolomide in metastatic malignant melanoma may predict long-term response for this treatment.

Can serial monitoring of serum Vascular Endothelial Growth Factor (VEGF), Nitric Oxide (NO), and Angiotensin II (ANGII) levels have predictive role during Bevacizumab treatment?

Background Standard treatment of colorectal cancer includes both cytostatic chemotherapy and targeted therapies. Bevacizumab, targeting the VEGF receptor, is one of the primary targeted therapies that achieve better response rate and survival rate as compared to combination chemotherapy. To the best of our knowledge, there is no established single marker that can be used as a predictive marker in bevacizumab therapy. Material/Methods We enrolled 24 patients with the diagnosis of metastatic colorectal cancer in our study. During the study, 2 blood samples were drawn from patients before the first cycle and after the sixth cycle of bevacizumab therapy. Serum levels of VEGF, ANG II, and NO were recorded. Results While the change across VEGF levels was found to be a statistically significant decreasing trend (p=0.009), this decrease was not found to be correlated with treatment response and hypertension development. Additionally, no statistically significant difference was found in terms of NO and ANG II levels. Conclusions This study showed a significant decrease in serum VEGF, but failed to show a significant change in NO and ANG II levels during bevacizumab treatment. Although no significant correlation was found between the presence of hypertension and markers, most patients (83%) had an increase in their blood pressure. Our results suggest that dynamic monitoring of NO and ANG II, along with VEGF, may not be useful as predictive markers for bevacizumab treatment in colorectal cancer.

Adjuvant uzatılmış temozolamid tedavisinin glioblastoma multiforme hastalarının sağkalımına etkisi

Amac: Retrospektif bu calismanin amaci cerrahi/biyopsi ile glioblastoma multiforme tanisi almis, kemoradyoterapi uygulanmis hastalarda uzatilmis temozolamid kullaniminin genel ve progresyonsuz sagkalim etkisini arastirmak olarak belirlendi. Gerec ve Yontem: Klinigimize basvuran cerrahi/biyopsi ile glioblastoma multiforme tanisi almis 225 hastadan, temozolamid ile birlikte radyoterapi tedavisi uygulandiktan sonra, ≤6 ay ve >6 ay sureyle adjuvan temozolamid kemoterapisi uygulanmis 116 hastatedavi toleransi, genel ve progresyonsuz sagkalimlari arasindaki farklar retrospektif olarak incelendi. Bulgular: Hastalarin ortalama takip suresi 18 ay (2-125 ay) olarak belirlenirken, 65(%56) hasta halen hayattadir. Uzatilmis temozolamid (>6 ay) olan grupta genel sagkalim daha uzun tespit edilirken istatistiksel bir fark tek degiskenli analizde tespit edilememistir sirasiyla 49.0 (≤6)vs 68.33 ay(>6). Ancak progresyonsuz sagkalim suresi uzatilmis temozolamid grubunda standart temozolamid alan gruba gore istatistiksel olarak anlamli oranda uzun saptanmistir 14 (>6)vs 9 ay(≤6). Gruplar arasinda anlamli bir yan etki farkliligi gorulmemistir. Sonuc: Calismamizda glioblastoma multiforme tanisi almis hastalarda uzatilmis temozolamid kullanimi hastalarin progresyonsuz sagkalim ve genel sagkalimlarinin belirgin oranda artmasina neden olur.

The prevalence of depression in patients with cancer in Jordan.

To the editor: We have read the article by Mhaidat et al. with great interest [1]. We suggest the paper by Mhaidat et al., however, it may be mitigated by some methodological weaknesses. The study was apparently designed to answer one question: “What is the prevalence of depression among patients with cancer in Jordan?”. The authors found that depression prevalence was 51.9% among cancer patients, and they emphasized that increased likelihood of depression was detected in patients who knew about their diagnosis and in those with advanced disease stages. They also added that more attention should have been paid in these subgroups. Our concern with Mhaidat et al.s paper is its presentation as a “national survey”. This study recruited 208 patients. This small sample size does not suggest a representative, national survey, in our opinion. Indeed, Mhaidat and colleagues cited other cross-sectional studies with significantly larger sample sizes of 456 and 930 patients, respectively [2, 3]. When we search for “national survey in cancer patients” in literature, we can find that these studies had more than a 1,000 patients. For example, a study on “Physical Activity, and Health-Related Quality Of Life in Cancer Survivors” from Canada, which has a population of 30 million according to Globocan 2002, included over 3,000 patients [4]. According to Globocan 2002 [5], Hashemite Kingdom of Jordan has a population about 5 million. For a study to be presented as a national survey, it must represent responses from people or units from the country as whole, not just from one clinic or institution. The chance of responding to that survey must be made available to the majority or all of the institutions, and the response rate must ideally be high enough to cover roughly around at least one third of all the possible respondents, as can be observed in the very recent examples from Belgium, France, USA, Great Britain, and Sweden [6–10]. In conclusion, although this valuable study contributes to knowledge on depression in Jordanian cancer patients, we feel that it falls short of a “national survey.”