Prognostic significance of early complete response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy: Multicentric study of Turkish Society for Radiation Oncology Group (TROD).

BACKGROUND/AIMS: To assess the effect of various parameters on the oncologic outcomes, including the time interval between therapy and surgery (S) in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: The data of 914 LARC patients who received preoperative CRT between 1994 and 2015 were collected retrospectively. Patients received 45-50.4 Gy RT with 5FU based chemotherapy (CT). They all underwent radical resection followed by maintenance CT. Clinical and pathologic variables were compared between the pCR and no-pCR groups. Survival was estimated by the Kaplan-Meier method and Cox proportional hazard model was used in multivariate analysis. RESULTS: After median follow-up of 60.5 (range=12-297.6) months, median overall survival (OS) was 58.75 months and disease-free survival (DFS) 53.32 months. pCR was observed in 18.9% of all cases. pCR, lymphovascular invasion and metastatic lymph node ratio (mLNR) were significantly associated with OS and DFS on multivariate analysis. The 5-year OS and DFS rates were better in pCR group (95.3% vs 80.7% for OS, p<0.0001 and 87.4% vs 71% for DFS, p<0.0001). pCR patients with 4-8 weeks interval had lower rates of distant metastasis (9% vs 20%, p=0.01) and any recurrences (13.6% vs 29.6%, p=0.001) than the remaining. Both OS and DFS were better in favor of pCR achieved at 4-8 week interval time (p<0.0001 for each). CONCLUSION: pCR after preoperative CRT in LARC correlated with better oncologic outcome. The best OS and DFS durations were achieved in patients who experienced pCR after 4-8-weeks interval before surgery.

Risk factors of radiation pneumonitis in patients with NSCLC treated with concomitant chemoradiotherapy--Are we underestimating diabetes?--Turkish oncology group (TOG)/Lung cancer study group.

INTRODUCTION: To evaluate the clinical and dosimetric parameters that increase the risk of radiation pneumonitis (RP) in locally advanced non-small cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy of nationwide multicentric data analysis. METHODS: All data of 268 patients who underwent definitive chemoradiotherapy were retrospectively collected from eight institutes participating in this study. Patient, tumor and treatment-related factors and dosimetric parameters were analyzed for grade ≥2 RP. The toxicity scoring system of The Radiation Therapy Oncology Group used for grading the severity of pneumonitis. A relationship with the risk of RP with potential predictive factors were evaluated by univariate and multivariate analyses. A recursive partition analysis (RPA) was applied to stratify patients according to the risk of developing RP. RESULTS: There were 90 (33.6%) patients who had grade ≥2 RP. The median time to pneumonitis after treatment was 4 months (range:1-6 months). In univariate analysis, diabetes mellitus (DM), use of cisplatin/etoposide, total and daily radiotherapy (RT) fraction dose, the planning target volume (PTV) size, mean lung dose, V5, V10 and RT technique were associated with the development of pneumonitis. In multivariate analysis, only DM (P = 0.008) was found to be independent risk factors for RP. According to RPA, the risk of developing RP was highest in patients with DM. CONCLUSIONS: In our study, besides the known dosimetric factors, DM was found to be the most important risk factor causing RP development in multivariate analysis and RPA. The risk is tripled compared to patients without DM.

Circulating gelatinases are not prognostic of treatment response and survival in locally advanced rectal cancer patients undergoing preoperative chemoradiotherapy.

PURPOSE: To investigate whether the serum levels of matrix metalloproteinases (MMPs) are predictive on treatment response and survival in locally advanced rectal cancer (LARC) patients undergoing preoperative chemoradiotherapy. PATIENTS AND METHODS: Serum MMP-2 and MMP-9 was analyzed by enzyme-linked immunosorbent assay and obtained before, midway, and 1-month after the end of preoperative radiotherapy treatment. The prognostic significance of serum MMP-2 and MMP-9 levels and their association with other pathological findings for LARC patients were evaluated. RESULTS: Serum levels of MMP-2 or MMP-9 were found to decrease with increasing clinical stage and negative correlation was statistically significant (P < 0.05). There was no statistically significant difference in tumor response and survival between the low and high MMP-2 and MMP-9 groups. MMP-2 and MMP-9 were not correlated with local-regional recurrence. CONCLUSIONS: We propose that serum levels of MMP-2 and MMP-9 are not predictive on treatment response and survival in LARC patients.

Intensity-Modulated Radiation Therapy Improves the Target Coverage Over 3-D Planning While Meeting Lung Tolerance Doses for All Patients With Malignant Pleural Mesothelioma.

PURPOSE: To investigate high conformality on target coverage and the ability on creating strict lung dose limitation of intensity-modulated radiation therapy in malignant pleural mesothelioma. PATIENTS AND METHODS: Twenty-four radiation therapy plannings were evaluated and compared with dosimetric outcomes of conformal radiation therapy and intensity-modulated radiation therapy. Hemithoracal radiation therapy was performed on 12 patients with a fraction of 1.8 Gy to a total dose of 50.4 Gy. All organs at risk were contoured. Radiotherapy plannings were differed according to the technique; conformal radiation therapy was planned with conventionally combined photon-electron fields, and intensity-modulated radiation therapy was planned with 7 to 9 radiation beam angles optimized in inverse planning. Strict dose-volume constraints were applied. RESULTS: Intensity-modulated radiation therapy was statistically superior in target coverage and dose homogeneity (intensity-modulated radiation therapy-planning target volume 95 mean 100%; 3-dimensional conformal radiation therapy-planning target volume 95 mean 71.29%, P = .0001; intensity-modulated radiation therapy-planning target volume 105 mean 11.14%; 3-dimensional conformal radiation therapy-planning target volume 105 mean 35.69%, P = .001). The dosimetric results of the remaining lung was below the limitations on intensity-modulated radiation therapy planning data (intensity-modulated radiation therapy-lung mean dose mean 7.5 [range: 5.6%-8.5%]; intensity-modulated radiation therapy-lung V5 mean 55.55% [range: 47%-59.9%]; intensity-modulated radiation therapy-lung V20 mean 4.5% [range: 0.5%-9.5%]; intensity-modulated radiation therapy-lung V13 mean 13.43% [range: 4.2%-22.9%]). CONCLUSION: With a complex and large target volume of malignant pleural mesothelioma, intensity-modulated radiation therapy has the ability to deliver efficient tumoricidal radiation dose within the safe dose limits of the remaining lung tissue.

Is there any impact of PET/CT on radiotherapy planning in rectal cancer patients undergoing preoperative IMRT?

BACKGROUND/AIM: To investigate the effect of positron emission tomography-computed tomography (PET/CT)-based contouring on dosimetric parameters in rectal cancer patients undergoing preoperative intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: Preoperative radiation therapy plans with conformal radiotherapy (CRT) or IMRT were created and examined according to the CT- and PET/CT-based contouring of 20 rectal cancer patients, retrospectively. RESULTS: The target volumes delineated with PET/CT were significantlylarger than the volumes created by CT (P= 0.043). Dose delivered to 98% of the planning target volume was high in IMRT planning contouring with CT and PET/CT compared with CRT planning, but the difference was not statistically significant (P = 0.056). Percent volumes receiving 105% of dose and 110% of dose were low in IMRT planning when compared with CRT (P < 0.0001 and P = 0.044, respectively). The volumes receiving 45 Gy for the small intestine, femur heads, and bladder and the maximum dose received by the bladder were significantly lower in IMRT. CONCLUSION: We showed that the target volumes created with PET/CT are significantly larger than the target volumes created with CT and that IMRT provides lower radiation exposure to the tumor-free tissues compared to the CRT planning. The dosimetric results primarily favor IMRT planning in rectal cancer patients and consequently present the significant alteration in target volumes.

Estimating radiation therapy toxicity and tolerability with comprehensive assessment parameters in geriatric cancer patients.

Cancer prevalance and incidence is increasing with aging of populations and age is a critical factor in decision-making for anti-cancer treatment. However it is believed that chronological age is not enough to guide management in elderly cancer patients. Multidisciplinary evaluation and comprehensive geriatric assessment has gained importance regarding the treatment selection especially for definitive anti-cancer therapy recently. We here aimed to analyse the effect of the comprehensive geriatric assessment parameters on radiotherapy toxicity and tolerability in a series of geriatric cancer patients in Turkey.

Prognostic significance of expression of CD133 and Ki-67 in gastric cancer.

CD133 is one of the most important stem cell markers in solid cancers and Ki-67 is a marker that reflects cell proliferation. The relationships between the expression of CD133 and Ki-67 and prognosis in gastric carcinoma are unknown and need exploring. We examined 50 gastric cancer patients retrospectively in the Radiation Oncology Department of the Faculty of Medicine, Gazi University. CD133 and Ki-67 expression was examined using immunohistochemical staining. The survival rate in patients with CD133 positive expression was significantly worse than that in the patients with negative expression (p=0.04). Expression of CD133 had a positive correlation with that of Ki-67 (r=0.350; p=0.014). Multivariate analysis revealed that the expression of CD133 was an independent prognostic factor in gastric cancer (p=0.02). Conclusion, expression of CD133 may be a useful prognostic marker in gastric cancer.

The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG).

Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5-92), and the mean survival was 25.8 months (95 % CI 20.4-29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27-4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities.

Clinical significance of lymph node ratio in locally advanced breast cancer molecular subtypes.

BACKGROUND: The ratio of metastatic to dissected lymph nodes (lymph node ratio; LNR) is a sensitive and superior prognostic factor for lymph node evaluation, but its relationship to cancer subtypes is unclear. PATIENTS AND METHODS: Data from 469 patients with axillary lymph node metastasis out of 640 early breast cancer cases were retrospectively analyzed. They were classified into 4 molecular subtypes; luminal A, luminal B HER2(+), HER2 overexpression, basal-like. LNRs were compared between groups and with other prognostic factors. RESULTS: The distribution of LNRs was 35.2% in luminal A, 43.2% in luminal B HER2(+), 46.9% in HER2 over-expression, and 39.1% in basal-like. A significant difference was found between luminal A and HER2 over-expression subtypes (p = 0.023). LNR was significantly correlated with tumor size and lymphovascular invasion, but not with other prognostic factors including menopausal status, laterality, grade, and perineural invasion. An LNR of 29.8% was defined as the cut-off value, and significant differences in survival rates were identified accordingly between basal-like and both luminal A (p = 0.003) and luminal B HER2(+) (p = 0.04). CONCLUSION: The LNR differs between some molecular subtypes of breast cancer, and it correlates with certain prognostic factors and survival. These data support using the LNR to assess breast cancer patients.

Smoking habits of relatives of patients with cancer: cancer diagnosis in the family is an important teachable moment for smoking cessation.

BACKGROUND: In this study we aimed to determine the rate and habitual patterns of smoking, intentions of cessation, dependence levels and sociodemographic characteristics of relatives of patients with a diagnosis of cancer. MATERIALS AND METHODS: This study was designed by the Turkish Oncology Group, Epidemiology and Prevention Subgroup. The relatives of cancer patients were asked to fill a questionnaire and Fagerstrom test of nicotine dependence. RESULTS: The median ages of those with lower and higher Fagerstrom scores were 40 years and 42 years, respectively. We found no evidence of variation between the two groups for the remaining sociodemographic variables, including the subject's medical status, gender, living in the same house with the patient, their educational status, their family income, closeness to their cancer patients or spending time with them or getting any help or wanting to get some help. Only 2% of the subjects started smoking after cancer was diagnosed in their loved ones and almost 20% of subjects had quit smoking during the previous year. CONCLUSIONS: The Fagerstrom score is helpful in determining who would be the most likely to benefit from a cigarette smoking cessation program. Identification of these people with proper screening methods might help us to pinpoint who would benefit most from these programs.

Impact of adjuvant chemoradiotherapy for rectal cancer on the long-term quality of life and late side effects: a multicentric clinical evaluation by the Turkish Oncology Group.

AIM: Although preoperative chemoradiatherapy (CRT) has proven its benefits in terms of decreased toxicity, there is still a considerable amount of cases that do not receive postoperative CRT. Oncologists at different geographic locations still need to know the long-term effects of this treatment in order to manage patients successfully. The current paper reports on long-term quality of life (QOL) and late side effects after adjuvant CRT in rectal cancer patients from 5 centers in Anatolia. METHODS: Rectal cancer patients treated with postoperative CRT with minimum 1-year follow-up and were in complete remission, were evaluated according to RTOG and LENT-SOMA scales. They were also asked to complete Turkish version of EORTCQLQ-C30 questionnaire and the CR-38 module. Each center participated with the required clinical data. RESULTS: Two hundred and thirty patients with median age of 55 years participated and completed the study. Median follow-up time was 5 years. All patients received RT concomitant with chemotherapy. Common parameters that both increased functional health scales and yielded better symptom scores were long term interval after treatment and sphincter-saving surgery. In addition, surgery type and follow-up time were determined to be predictors of QOL scores and late toxicity grade. CONCLUSION: Postoperative CRT was found to have a great impact on the long term QOL and side effects in rectal cancer survivors. The factors that adversely affect these are abdominoperineal resection and shorter interval. The findings may encourage life-long follow-up and cooperation with patients, which should be mentioned during the initial counseling.

Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy.

PURPOSE: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. METHODS AND MATERIALS: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primary endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. RESULTS: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. CONCLUSIONS: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.

Uterine lipoleiomyoma containing metastatic breast carcinoma: a case with two unusual pathologies.

Uterine lipoleiomyoma is a rare benign tumor. Besides this, metastasis to this tumor from breast carcinoma is extremely rare without any case reported in the literature. We report one such case of metastatic carcinoma in uterine lipoleiomyoma from primary breast cancer.