A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy.

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.

Efficacy of adjuvant capecitabine in residual triple negative breast cancer: a multicenter observational Turkish Oncology Group (TOG) study.

BACKGROUND: Triple negative breast cancer (TNBC) is characterized by high rates of recurrence, especially in patients with residual disease after neoadjuvant chemotherapy (NAC). Capecitabine is being used as standard adjuvant treatment in residual TNBC. We aimed to investigate the real-life data regarding the efficacy of capecitabine in residual TNBC. DESIGN AND METHODS: In this retrospective multicenter study, TNBC patients with residual disease were evaluated. Patients, who received standard anthracycline and taxane-based NAC and adjuvant capecitabine were eligible. Overall survival (OS), disease free survival (DFS) and toxicity were analyzed. RESULTS: 170 TNBC patients with residual disease were included. Of these, 62.9% were premenopausal. At the time of analysis, the recurrence rate was 30% and death rate was 18%. The 3-year DFS and OS were 66% and 74%, respectively. In patients treated with adjuvant capecitabine, residual node positive disease stood out as an independent predictor of DFS (p = 0.024) and OS (p = 0.032). Undergoing mastectomy and the presence of T2 residual tumor was independent predictors of DFS (p = 0.016) and OS (p = 0.006), respectively. CONCLUSION: The efficacy of capecitabine was found lower compared to previous studies. Selected patients may have further benefit from addition of capecitabine. The toxicity associated with capecitabine was found lower than anticipated.

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.

Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group.

Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.

Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study.

OBJECTIVES: To compare the survival of first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as first line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study. RESULTS: EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p = 0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p = 0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically significant (p = 0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically different than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p = 0.323). CONCLUSION: In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both first- and second-generation EGFR-TKIs should be considered, especially as first- and second-line options.

Validation of bioelectrical impedance analysis in the evaluation of body composition in patients with breast cancer.

BACKGROUND: The evaluation of body composition is an essential parameter for preventing obesity and sarcopenic obesity, which are prognostic factors in breast cancer. This study aims to validate the bioelectrical impedance analysis (BIA) of women who are breast cancer survivors by using the dual-energy x-ray absorptiometry (DXA) measurement method. METHODS: This validation study included 104 women without metastasis between 32 and 72 years old (mean 47.03 ± 8.59) whose treatment was completed 6 months prior. Body composition analysis was performed sequentially using both measurements and when participants were hungry. RESULTS: Meaningful differences were found in fat-free mass (FFM) (BIA: 46.57 ± 5.54 kg; DXA: 41.06 ± 5.11 kg), body fat percentage (%BF) (BIA: 34.28% ± 6.24%; DXA: 43.91% ± 5.58%), body fat mass (FM) (BIA: 25.37 ± 8.84 kg; DXA: 31.24 ± 9.09 kg), and lean soft tissue mass (LSTM) (BIA: 4.42 ± 5.66 kg; DXA: 38.75 ± 4.98 kg) (P < 0.001). Powerful associations for body FM and strong associations for other parameters were seen. A constant and/or proportional error was found between the two devices within the direction of strong and solid components. Compared with DXA, the BIA measurement gives a lower estimate of %BF and FM and a higher estimate of LSTM and FFM. CONCLUSIONS: By the mathematical relationship between the two measurement methods, it seems possible to adapt the body composition parameters obtained from BIA of patients with breast cancer to DXA results. In the future, there will be a need to evaluate these two devices with more extensive studies.

Coronaphobia: A barrier to ongoing cancer treatment?

INTRODUCTION: Increased stress levels caused by the pandemic might cause delays in cancer treatment. We conducted a survey among cancer patients undergoing treatment to evaluate their psychological wellbeing and treatment adherence during Coronavirus disease 19 (COVID-19) pandemic. MATERIAL AND METHODS: Patients receiving active chemotherapy at a private oncology center between January and May 2021 were included. Healthy volunteers were employees of a district health directorate with no history of cancer or chronic disease. Treatment adherence was described as compliant if the prescribed treatment was received within a week and the information was gained from patient charts. Hospital anxiety and depression scale (HADS) and COVID-19 phobia scale (CP19-S) were administered to participants. RESULTS: 402 participants were included; 193 (48%) were cancer patients. The mean age of the participants was 44 years old and 68% of the participants were female. All participants' CP19-S mean score was 47.9. Patient group had significantly lower CP19-S (p = 0.006). Chronic disease and history of a shocking event were the factors associated with CP19-S. All participants reporting hospital anxiety were found to have significantly higher COVID-19 phobia levels (p < 0.05). Patients' mean HADS-anxiety score was significantly higher (7.3 vs. 6.5, p = 0.027). COVID-19 phobia was an independent factor increasing the level of anxiety and depression in both groups. Adherence to treatment was 100%. CONCLUSION: The pandemic increased levels of anxiety, however, cancer treatment continued to be a priority in patients' lives. Strategies should be developed to support oncology patients cope with the pandemic and increase their courage to avoid treatment delays.

The role of adjuvant chemotherapy in resected stage I non - small cell lung cancer: A Turkish Oncology Group Study.

PURPOSE: The benefit of adjuvant chemotherapy for tumors smaller than 4 cm is not clear. We aimed to evaluate the prognostic impact of adjuvant platin-based chemotherapy in high-risk stage I patients with non-small cell lung cancer (NSCLC). METHODS: This cooperative group study included 232 NSCLC patients who underwent curative surgery for stage I disease with tumor size 2-4 cm. Re ults: Median age at presentation was 63 years (range 18-90). The mean tumor size was 29.6 ± 7.3 mm. The frequency of patients with specified risk factors were: visceral pleural effusion (VPI): n: 82 (36.6%); lymphovascular invasion (LVI): n: 86 (39.1%); Grade 3: n: 48 (32.7%); Solid micropapillary pattern (SMP): n: 70 (48.3%). Adjuvant platin-based chemotherapy was administered to 51 patients. During a median follow-up period of 50.5 months 68 patients (29.3%) developed recurrence, 54 (23.3%) died from any cause and 38 (16.4%) of them died of lung cancer. Patients who received chemotherapy compared with the non-chemotherapy group had a longer 5-years relapse-free survival (RFS) (84.5 vs 61.1%). Also on multivariate analysis, adjuvant chemotherapy was a significant independent prognostic factor for RFS. CONCLUSION: Adjuvant platin-based chemotherapy should be considered for patients with small tumors with adverse risk factors. Key words: adjuvant chemotherapy, lung cancer, oncology, lymphovascular invasion, solid-micropapillary pattern, platinum-based therapy.

Turkish national consensus on breast cancer management during temporary state of emergency due to COVID-19 outbreak.

OBJECTIVES: Cancer care is excessively influenced by the COVID-19 outbreak for various reasons. One of the major concerns is the tendency for delayed surgical treatment of breast cancer patients. The outbreak has urged clinicians to find alternative treatments until surgery is deemed to be feasible and safe. Here in this paper, we report the results of a consensus procedure which aimed to provide an expert opinion-led guideline for breast cancer management during the COVID-19 outbreak in Turkey. MATERIAL AND METHODS: We used the Delphi method with a 9-scale Likert scale on two rounds of voting from 51 experienced surgeons and medical oncologists who had the necessary skills and experience in breast cancer management. Voting was done electronically in which a questionnaire-formatted form was used. RESULTS: Overall, 46 statements on 28 different case scenarios were voted. In the first round, 37 statements reached a consensus as either endorsement or rejection, nine were put into voting in the second round since they did not reach the necessary decision threshold. At the end of two rounds, for 14 cases scenarios, a statement was endorsed as a recommendation for each. Thirty-two statements for the remaining 14 were rejected. CONCLUSION: There was a general consensus for administering neoadjuvant systemic therapy in patients with node-negative, small-size triple negative, HER2-positive and luminal A-like tumors until conditions are improved for due surgical treatment. Panelists also reached a consensus to extend the systemic treatment for patients with HER2-positive and luminal B-like tumors who had clinical complete response after neoadjuvant systemic therapy.

Bilateral synchronous adrenal metastasis of invasive ductal carcinoma treated with multimodality therapy including adrenalectomy and oophorectomy.

A 38-year-old woman presented with a mass in the left breast. Biopsy of the lesion revealed invasive ductal carcinoma. Bilateral adrenal metastasis was detected in whole body positron emission tomography scanning. Needle biopsy of the left adrenal lesion proved infiltration of malignant cells from breast carcinoma. After eight cycles of neoadjuvant (preoperative) chemotherapy, mastectomy, bilateral adrenalectomy, and bilateral oopherectomy were performed. No further hormonal treatment was recommended due to the resection of both adrenal glands and ovaries. The patient is still followed without any sign of progression. To our knowledge, this is the first case representing multimodality approach to breast cancer with bilateral synchronous adrenal metastasis. Patients with oligometastatic disease may benefit from aggressive treatment including local therapies.

Safety, Feasibility, and Efficacy of Capecitabine Maintenance in Patients With Advanced Gastric Cancer: A Retrospective Study.

Gastric cancer is still one of the cancers with highest mortality. Most patients present with advanced-stage disease. Palliative chemotherapy is usually the only treatment option for patients with advanced gastric cancer (AGC). Maintenance chemotherapy is an evolving concept in medical oncology. Maintenance chemotherapy can be administered with the same drug(s) in the initial regimen or with an alternative agent. In this article, we report our experience with capecitabine as a maintenance agent for patients with AGC. No treatment-related death was observed due to use of capecitabine. Median progression-free survival was 10.4 months, and median overall survival was 19.7 months. Activity and toxicity profile of capecitabine seems favorable as a maintenance agent in AGC. We believe that capecitabine deserves further trials as a maintenance agent for patients with AGC.

Cutaneous melanoma in Turkey: analysis of 1157 patients in the Melanoma Turkish Study.

PURPOSE: To develop a large Turkish National Melanoma registry in order to define demographic and clinicopathologic characteristics of patients with melanoma. METHODS: The data was collected from 1635 patients with melanoma through a web-based registry system in 22 centers. Herein we present the results of 1157 patients with cutaneous melanoma. RESULTS: The patient median age was 56.4 years and 646 (55.8%) were males. The commonest subtype was superficial spreading type (357, 30.9%). The commonest primary site was the lower extremities (N=353, 30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only 104 (12.5%) patients had a thickness <1mm. Among 694 patients with available data, 136 (19.6%) presented with stage 4 disease while the most frequent stage was stage 3, encountered in 393 (56.6% patients). CONCLUSION: Our melanoma registry is the largest in our country providing a snapshot view of cutaneous melanoma and its care. Our patients presented with more advanced stages and they had worse prognosis compared to SEER database.

Revisiting post-gastrectomy anemia with a brief survey among a group of Turkish medical oncologists.

PURPOSE: Total or subtotal gastrectomy are performed as curative or palliative treatment in patients with gastric cancer. Anemia is a frequent complication of gastrectomy. Patients undergoing total or subtotal gastrectomy should be carefully monitored for the development of anemia and be given appropriate treatment when indicated. This survey-based study aimed to determine the level of knowledge about post-gastrectomy anemia in Turkish medical oncologists. METHODS: The study included 110 Turkish medical oncologists that agreed voluntarily to participate in the survey and answer an 8-item questionnaire. The survey was distributed as a questionnaire during the 5th Turkish Medical Oncology Congress in March 2014. RESULTS: All participants completed the questionnaire. Most of the participants would not recommend oral iron or cobalamin replacement after gastrectomy. CONCLUSION: The results of the survey indicate that Turkish medical oncologists have some knowledge about post-gastrectomy anemia, but need to learn more about appropriate follow-up and replacement therapies for post-gastrectomy anemia.

Comparison of metabolic and anatomic response to chemotherapy based on PERCIST and RECIST in patients with advanced stage non-small cell lung cancer.

BACKGROUND: The aim of this study was to explore the prognostic role of metabolic response to chemotherapy, determined by FDG-PET, in patients with metastatic non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Thirty patients with metastatic NSCLC were analyzed for prognostic factors related to overall survival (OS) and progression free survival (PFS). Disease evaluation was conducted with FDG-PET/CT and contrast-enhanced CT prior to and at the end of first-line chemotherapy. Response evaluation of 19 of 30 patients was also performed after 2-3 cycles of chemotherapy. Morphological and metabolic responses were assessed according to RECIST and PERCIST, respectively. RESULTS: The median OS and PFS were 11 months and 6.2 months, respectively. At the end of first-line chemotherapy, 10 patients achieved metabolic and anatomic responses. Of the 19 patients who had an interim response analysis after 2-3 cycles of chemotherapy, 3 achieved an anatomic response, while 9 achieved a metabolic response. In univariate analyses, favorable prognostic factors for OS were number of cycles of first-line chemotherapy, and achieving a response to chemotherapy at completion of therapy according to the PERCIST and RECIST. The OS of patients with a metabolic response after 2-3 cycles of chemotherapy was also significantly extended. Anatomic response at interim analysis did not predict OS, probably due to few patients with anatomic response. In multivariate analyses, metabolic response after completion of therapy was an independent prognostic factor for OS. CONCLUSIONS: Metabolic response is at least as effective as anatomic response in predicting survival. Metabolic response may be an earlier predictive factor for treatment response and OS in NSCLC patients.

Voltage-gated sodium channel blockers can augment the efficacy of chemotherapeutics by their inhibitory effect on epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a process during which cancer cells become more invasive and chemo resistant. EMT may also be associated with tumor dormancy which prevents the cure of cancer with adjuvant treatment. Chemo resistance and dormancy may also decrease response to cytotoxic agents during treatment of metastatic disease. Voltage gated sodium channels (VGSCs) are overexpressed in many cancer types, particularly in those with more aggressive and metastatic potential. VGSCs are thought to be associated with increased invasive and migratory capacity of cancer cells. Inhibition of VGSCs may inhibit EMT and angiogenesis through interaction with intracellular calcium activity and endothelial cells respectively. Blockage of these channels combined with other anticancer therapies may be effective in both adjuvant and palliative setting. Colonization at secondary site may be decelerated by VGSCs inhibition through impeding angiogenesis. This may lead to a temporary palliation of symptoms related to tumor burden in patients with metastatic disease.

Development of acute pulmonary hypertension after bortezomib treatment in a patient with multiple myeloma: a case report and the review of the literature.

Bortezomib is widely used in treatment of multiple myeloma. In recent years, severe bortezomib-induced lung injury has been reported. The clinical course is generally characterized with fever and dyspnea, followed by respiratory failure with pulmonary infiltrates. Herein, we report a 57-year-old man with newly diagnosed multiple myeloma admitted with dyspnea, fever, and hypotension on the third day of the first dose of bortezomib therapy. He had bilateral jugular venous distention, crackles at the bases of the lungs and hepatomegaly. Transthoracic echocardiography revealed acute pulmonary hypertension (PH) with an estimated pressure of 70 mm Hg. The perfusion scintigraphy ruled out pulmonary embolism, and microbiological examination was negative. On his course, fever, dyspnea, hypoxia, and pulmonary vascular pressure subsided rapidly. The sudden onset of PH and its rapid decrement without any treatment suggests bortezomib as the underlying cause. Subsequently, the patient did not respond to vincristine-doxorubicin-dexamethasone regimen and thalidomide. Bortezomib treatment was repeated, and no pulmonary adverse reactions occurred. Follow-up echocardiographies revealed pulmonary arterial pressures to be maximally of 35 mm Hg. To our knowledge, this is the first case of acute PH after front-line bortezomib therapy. In this report, we review bortezomib-related pulmonary complications in the literature and possible underlying mechanisms.