Erdafitinib-Induced Bilateral Multifocal Serous Retinal Detachments and Severe Dry Eye Related Unilateral Peripheral Ulcerative Keratitis in a Patient with Metastatic Urothelial Carcinoma.

Background: A case of bilateral multifocal serous retinal detachments and dry eye complicated with unilateral peripheral ulcerative keratitis (PUK) during erdafitinib therapy is described. Case description: A 76-year-old male underwent a baseline examination two months after initiating 8 mg erdafitinib therapy (April 2023) due to metastatic urothelial carcinoma. Left subfoveal serous retinal detachment was observed initially but the treatment was resumed as he was asymptomatic. In May 2023, bilateral multifocal subretinal fluid pockets were identified, and the patient was still asymptomatic. However, in June 2023 he complained of bilateral redness and a stinging sensation in his right eye. Bilateral severe dry eye and right PUK were diagnosed. He was prescribed dexamethasone eye drops and sodium hyaluronate artificial tears for both eyes. One week later corneal staining decreased, and progression of PUK ceased. Erdafitinib therapy was discontinued in June 2023 due to the planned transurethral prostatectomy. By July 2023, after discontinuation of the drug and administration of the topical treatment, the dry eye improved and the PUK became inactive. There was also resolution of subretinal fluid pockets in the right eye and a reduction of subretinal fluid pockets in the left eye. After the reinitiation of erdafitinib therapy, serous retinal detachments recurred in both eyes in September 2023, but both corneas remained stable with topical low-dose dexamethasone, cyclosporine-A and artificial tear usage. Conclusion: Erdafitinib therapy may lead to concurrent anterior and posterior segment complications. Multidisciplinary monitoring is crucial for patients undergoing erdafitinib therapy to prevent possible visual disturbances. LEARNING POINTS: Erdafitinib, a tyrosine kinase inhibitor of fibroblast growth factor receptors 1 to 4, is administered for the treatment of locally advanced, unresectable or metastatic urothelial carcinoma but however is fraught with several systemic and ocular side effects.Concurrent anterior and posterior segment ocular involvement could be encountered in patients undergoing erdafitinib therapy.Maintaining a high level of suspicion and closely monitoring for potential ocular complications through collaborative efforts is essential for all patients undergoing erdafitinib therapy.

Evaluation of treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy accompanied by the G-8 geriatric score: TROD13-003 multicenter study.

INTRODUCTION: The choice of treatment for rectal cancer often differs in older and younger patients, with the rate of radiotherapy use lower among older adults. In our daily practice, when evaluating a frail older patient with rectal cancer, we usually choose to give less treatment. This may be due to concern that the patient will not be able to tolerate radiotherapy. The Geriatric 8 score (G8GS) is a guide to evaluating treatment tolerability as it relates to frailty in older adults with cancer. The aim of this study was to evaluate treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy (RT) accompanied by G8GS. MATERIALS AND METHODS: Patients aged 65 and older with stage I-III rectal adenocarcinoma who were treated with RT and had a G8 evaluation were included in this multicenter retrospective study. Prognostic factors related to G8GS were calculated using Chi-square and logistic regression tests and survival rates were calculated by the Kaplan-Meier test using the SPSS v24.0 software. All p-values ≤0.05 were considered statistically significant. RESULTS: A total of 699 patients from 16 national institutions were evaluated. The median age was 72 years (range 65-96), and the median follow-up was 43 (range 1-190) months. Four hundred and fifty patients (64%) were categorized as frail with G8GS ≤14 points. Frail patients had higher ages (p = 0.001) and more comorbidities (p = 0.001). Ability to receive concomitant and/or adjuvant chemotherapy rates were significantly higher in fit patients (p = 0.002 and p = 0.001, respectively). No significant difference was observed in terms of grade 3-4 early and late toxicity for both groups. Cancer-related death was higher (p = 0.003), and 5- and 8-year survival rates were significantly lower (p = 0.001), in the frail group. Age and being frail were significantly associated with survival. DISCUSSION: Radiotherapy is a tolerable and effective treatment option for older adults with rectal cancer even with low G8GS. Being in the frail group according to G8GS and having multiple comorbidities was negatively associated with survival. Addressing the medical needs of frail patients through a comprehensive geriatric assessment prior to radiotherapy may improve G8GS, allowing for standard treatment and increased survival rates.

Who would be the winner? A prognostic nomogram for predicting the benefit of postoperative radiotherapy ± chemotherapy in patients with locally advanced gastric cancer: TROD-02-01 study.

OBJECTIVES: We aimed to develop a basic, easily applicable nomogram to improve the survival prediction of the patients with stage II/III gastric cancer (GC) and to select the best candidate for postoperative radiotherapy (RT). METHODS: In this multicentric trial, we retrospectively evaluated the data of 1597 patients with stage II/III GC after curative gastrectomy followed by postoperative RT ± chemotherapy (CT). Patients were divided into a training set (n = 1307) and an external validation set (n = 290). Nomograms were created based on independent predictors identified by Cox regression analysis in the training set. The consistency index (C-index) and the calibration curve were used to evaluate the discriminative ability and accuracy of the nomogram. A nomogram was created based on the predictive model and the identified prognostic factors to predict 5-year cancer-specific survival (CSS) and progression-free survival (PFS). RESULTS: The multivariate Cox model recognized lymph node (LN) involvement status, lymphatic dissection (LD) width, and metastatic LN ratio as covariates associated with CSS. Depth of invasion, LN involvement status, LD width, metastatic LN ratio, and lymphovascular invasion were the factors associated with PFS. Calibration of the nomogram predicted both CSS and PFS corresponding closely with the actual results. In our validation set, discrimination was good (C-index, 0.76), and the predicted survival was within a 10% margin of ideal nomogram. CONCLUSIONS: In our relatively large cohort, we created and validated both CSS and PFS nomograms that could be useful for underdeveloped or developing countries rather than Korea and Japan, where the D2 gastrectomy is routinely performed. This could serve as a true map for oncologists who must make decisions without an experienced surgeon and a multidisciplinary tumor board.

Revisiting the Radical Radiotherapy-Radiochemotherapy Results in Anal Canal Cancers: (TROD Gastrointestinal Group Study 02-005).

BACKGROUND AND AIM: This study aimed to determine treatment outcomes and factors affecting prognosis in patients diagnosed with anal canal cancer who received radical radiotherapy (RT) or radiotherapy combined with chemotherapy (CT-RT) in radiation oncology centers in Turkey and compare the results with literature. MATERIAL AND METHOD: The study included 193 patients with anal canal cancer reported between 1995 and 2019, of which 162 had complete data. The study was conducted in 11 radiation oncology centers, and a joint database was shared among them. Patients received radiotherapy doses of 45 Gy to 60 Gy. Data analysis was done using SPSS for Windows version 20. RESULTS: Median follow-up was 48.51 months (2-214). All patients received radiotherapy, and 140 (86.4%) received concurrent chemotherapy. Radiotherapy doses of 50.4 Gy to 60 Gy were administered to 74 patients (45.7%) using 2-dimensional-3-dimensional (2D-3D) conformal therapy and 70 patients (43.2%) using intensity modulated radiotherapy technique (IMRT). Acute phase hematologic toxicity was observed in 62 patients (38.3%), and nonhematologic toxicity in 123 patients (75.9%). The 5-year overall survival (OS) rate was 75.1% and disease-specific survival (DSS) rate was 76.4%. OS without colostomy was achieved in 79,8 % at 5 years, and complete response in 112 patients (69.1%). OS rate was significantly higher in 142 patients with positive response (P < .000) and 112 with complete response (P < .000). Anemia (P < .002), local progression, and systemic progression (P < .000) resulted in lower OS (P < .002). In univariate analysis, factors affecting OS rate were: gender, age, stage, lymph node status, T stage, RT treatment duration, and treatment planning with PET fusion, which were found to be statistically significant. Completing radiotherapy in less than 45 days, concurrent chemotherapy, and continued administration of mitomycin and 5 FU as chemotherapy had a significant positive effect on overall survival. OS rate was higher in patients receiving RT dose of 58 Gy or less and undergoing IMRT planning in radiotherapy. IMRT was associated with lower acute and late side effects. CONCLUSION: Radiochemotherapy is the primary treatment for anal canal cancer and advanced radiotherapy techniques may increase survival by reducing side effects and improving treatment continuation. Higher treatment doses require further investigation. The efficacy of treatment can be improved by including patients treated with modern radiotherapy techniques in multicenter prospective studies using new and more effective chemotherapy and immunotherapy agents.

Diagnostic performance of magnetic resonance imaging in preoperative local staging of rectal cancer after neoadjuvant chemoradiotherapy

PURPOSE: This paper aims to investigate the diagnostic performance of magnetic resonance imaging (MRI) in predicting the pathologic stage of locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT) and the role of MRI in selecting patients with a pathologic complete response (ypCR). METHODS: Restaging MRI (yMRI) examinations of 136 patients with LARC treated with neoadjuvant CRT followed by surgery were retrospectively analyzed by two radiologists. All examinations were performed on a 1.5 Tesla MRI machine with a pelvic phased-array coil. T2-weighted turbo spin-echo images and diffusion-weighted imaging were obtained. Histopathologic reports of the surgical specimens were the reference standard. The accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) of yMRI in predicting the pathologic T-stage (ypT), N-stage, and ypCR were calculated. The inter-observer agreement was evaluated using kappa statistics. RESULTS: The yMRI results showed 67% accuracy, 59% sensitivity, 80% specificity, 81% PPV, and 56% NPV in identifying ypT (ypT0-2 versus ypT3-4). In predicting the nodal status, the yMRI results revealed 63% accuracy, 60% sensitivity, 65% specificity, 47% PPV, and 75% NPV. In predicting ypCR, the yMRI results showed 84% accuracy, 20% sensitivity, 92% specificity, 23% PPV, and 90% NPV. The kappa statistics revealed substantial agreement between the two radiologists. CONCLUSION: Utilization of yMRI showed high specificity and PPV in predicting the tumor stage and high NPV in predicting the nodal stage; in addition, yMRI revealed moderate accuracy in the T and N classifications, mainly due to underestimating the tumor stage and overestimating the nodal status. Finally, yMRI revealed high specificity and NPV but low sensitivity in predicting the complete response.

Evaluation of hereditary/familial breast cancer patients with multigene targeted next generation sequencing panel and MLPA analysis in Turkey.

Breast cancer, a worldwide leading cause of cancer in women, may occur in familial cases. Germline mutations in BRCA1/2 genes are responsible for 15% of the familial cases. With the power of next generation sequencing (NGS) analysis, it is possible to analyze genes related to hereditary susceptibility to breast cancer and investigate the genetic etiology more thoroughly. In this study, we investigated 30 genes identified frequent pathogenic alleles in Turkish population. The study includes 495 unrelated individuals diagnosed with breast cancer who are selected for genetic testing according to NCCN criteria for hereditary breast cancer. All patients were analyzed by NGS for BRCA1/2 genes. Deletion/duplication investigation by Multiplex ligation-dependent probe amplification (MLPA) and massive sequencing of 30 breast cancer-related genes (Oncorisk Gene Panel) were performed in a stepwise manner. BRCA1/2 variants are the most frequent pathogenic variants which are found in 45 of 495 (9.1%) patients. Four previously unreported, novel, pathogenic variants of BRCA2 gene are identified. In four cases, exonic deletions of BRCA1/2 genes are determined and there is no duplication of these genes. NGS panel investigation involving other moderate-high risk genes contributed genetic diagnosis in an extra 39 out of 419 (9.3%) cases. Our study presents the cost effectiveness of the gene panel approach. We suggest that gene panels should be the first-tier genetic testing for hereditary breast cancer and MLPA analysis of BRCA1/2 genes should be investigated as a complementary method of NGS analysis.

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.

Effects of Health Belief Model based nursing interventions offered at home visits on lymphedema prevention in women with breast cancer: A randomised controlled trial.

BACKGROUND: Lymphedema is an important morbidity due to its physical and psychological restrictions and financial burden in women having breast cancer surgery. The study was performed to examine effects of Health Belief Model (HBM) based nursing interventions given at home visits on prevention of lymphedema in women having breast surgery. DESIGN: The study had an experimental design. METHODS: The study included 72 women receiving radiotherapy after breast surgery, of whom 37 formed the intervention group and 35 formed the control group. The sample was based on Consolidated Standard of Reporting Trials (CONSORT). Data were collected with a personal information questionnaire, Quick-Disabilities of the Arm, Shoulder and Hand Score (Q-DASH), European Organization for Research and Treatment of Cancer Quality of Life for Breast Cancer 23 (EORTC QLQ-BR23), Strategies Used by Patients to Promote Health (SUPPH), Arm Circumference Form at three home visits at 3-month intervals. RESULTS: HBM based nursing interventions regularly offered at home visits were found to create positive changes in behaviour of lymphedema prevention and improve upper extremity functions, reduce side-effects, relieve arm and breast symptoms, enhance the quality of life, increase self-efficacy and lower the frequency of lymphedema and costs. CONCLUSION: The HBM based nursing interventions regularly offered at home visits can create positive changes in behaviour of lymphedema prevention and prevent lymphedema in women receiving radiotherapy after breast surgery. Considering costs of treatment for lymphedema, these interventions can be considered as cost-effective. RELEVANCE TO CLINICAL PRACTICE: Nursing interventions directed towards behaviour of preventing lymphedema and follow-ups in the long-term should be supported by home visits and reminders through phone calls. Nurses should perform HBM based interventions regularly at home visits to prevent lymphedema. These interventions were found to reduce financial burden and were cost-effective.

The importance of mesorectum motion in determining PTV margins in rectal cancer patients treated with neoadjuvant radiotherapy.

New precision radiotherapy (RT) techniques reduce the uncertainties in localizing soft and moving tumors. However, there are still many uncontrollable internal organ movements. In our study, patients who underwent neoadjuvant chemoradiotherapy (NA-CRT) for rectal cancer were evaluated to determine inter-fraction mesorectum motion and dosimetric changes. Fourteen patients treated with NA-CRT for rectal cancer between 2014 and 2016 were included in the analysis. The mesorectum and clinical target volume (CTV) were delineated on planning computed tomography (CT) and cone-beam CT (CB-CT) scans. After planning with a volumetric modulated arc therapy (VMAT) plan, re-planning was performed on all CB-CTs. Finally, the volumetric and dosimetric changes of PTV and mesorectum were evaluated in all CB-CTs compared with the initial CT and VMAT plans. The geometrical center of mesorectum volume in CB-CTs had moved 1 (0.2-6.6), 1.6 (0.2-3.8) and 1.6 (0-4.9) mm in the x, y and z-axis respectively compared with the initial CT. The dosimetric parameters of PTV including D2, D95 and D98 on CB-CT showed a median 47.19 (46.70-47.80), 45.05 (44.18-45.68) and 44.69 (43.83-45.48) Gy and median 1% (1-2), 0% (0-2) and 1% (0-2) dosimetric change compared with the initial VMAT plan. In our study, we have shown that the mesorectum has moved up to 20 mm in the lateral and anterior-posterior direction and almost 10 mm in the superior/inferior direction during RT, causing a median of ~2% change in dosimetric parameters. Therefore, these movements must be considered in determining PTV margins to avoid dosimetric changes.

Treatment results in patients with ductal carcinoma in situ treated with adjuvant radiotherapy

Background/aim: The aim of this study was to evaluate the treatment results of patients undergoing adjuvant radiotherapy (ART) after breast surgery with the diagnosis of ductal carcinoma in situ (DCIS). Materials and methods: A total of 61 women who had undergone radiotherapy following extensive surgical excision were enrolled. All patients underwent 50 Gy ART. Survival analysis was performed using Kaplan­Meier analysis and SPSS 20.0. Results: The median age was 52 years (range: 28­86). The median follow-up period after RT was 92 months (range: 23­237). The median overall survival and distant and regional recurrence-free and disease-specific survival was 96 months (range: 26­240), while disease-free and local recurrence-free survival was 96 months (range: 22­240). While the 15-year and 20-year overall survival rates were 87% and 87%, respectively, the recurrence-free survival rates were 98% and 98%, respectively; the rates of disease-specific survival were 100% and 100%, respectively. Conclusion: The results of this study with a long follow-up period have shown that ART in DCIS is an effective treatment method to provide local disease control. However, further large studies are needed to identify the prognostic factors.

Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

PURPOSE: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era. METHODS: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT. RESULTS: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5­year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10. CONCLUSIONS: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.

A heart atlas for breast radiation therapy and the influence of delination education on both intra and interobserver variability.

PURPOSE: We developed a heart atlas for breast radiation therapy and evaluated the influence of education on intra and inter-observer similarity, and cardiac dose reporting. MATERIALS AND METHODS: The data of 16 left breast cancer patients were analyzed. Eight observers delineated heart and cardiac subunits [left (LCA) and right (RCA) coronary arteries, left anterior descending artery (LAD), bilateral atrium and ventricles] before the education. A radiologist and radiation oncologist developed the atlas and delineated the gold standard (GS) volumes. Observers repeated the delineation after education. RT plans were made for pre/post-atlas contours. The similarity was assessed by Dice (DSC) and Jaccard (JSC) similarity coefficient indices. The absolute difference rate was calculated for the dose analysis. RESULTS: The inter-observer similarity increased in heart and all subunits. The intra-observer similarity showed a heterogeneous distribution. The absolute difference rate in dose reporting was statistically significant for the bilateral atrium, right ventricle, LAD, LCA + LAD, RCA's maximum doses (p < 0.05). The maximum dose reporting differences from the GS decreased from 16.9 to 8.9% for LAD (p = 0.011); from 14.8 to 9.3% for LCA + LAD (p = 0.010). CONCLUSION: The cardiac atlas reduces the intra-interobserver differences and improves dose reporting consistency. The first intra-observer similarity analysis was made in our study and revealed the need for repeated education to increase the consistency.

Prognostic Importance of Tumor Deposits in the Ipsilateral Axillary Region of Breast Cancer Patients.

Tumor deposits (TD) are irregular discrete tumor masses in adipose tissue, discontinuous from the primary tumor, that are described in various cancers. The incidence and/or prognostic value of TD in breast carcinomas have not been studied so far. We reevaluated 145 breast cancer patients, diagnosed and treated between 2001 and 2006 at our institution for the presence and incidence of TD. Histologic type, grade, size of the primary tumor, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 status of the tumor, and presence of peritumoral lymphovascular invasion were included in the data. TD were detected in 42 cases (29.0%). The mean age of the patients was 52.2 years (27-82). Most patients (79.3%) had either invasive carcinoma of no special type (NST) or invasive lobular carcinoma, and most tumors (86.9%) were either grade 2 or 3. After excluding TD from the number of metastatic lymph nodes, the pN status of 9 patients changed. Univariate analysis of 110 patients with follow-up information revealed that the new pN status (p = 0.036), presence of local recurrence (p = 0.016) and TD (p = 0.003) were significantly correlated with distant metastases. The median follow-up of the patients was 84 months (5-161), 10-year disease-free survival and overall survival were 67.2% and 73.7%, respectively. In multivariate analysis, presence of TD remained independently associated with distant metastasis (p = 0.002). The probability of distant metastasis was 3.3 times higher in patients with TD. These results emphasize that TD are present in breast cancer patients, and that their presence should warn the clinician in terms of possible distant metastasis. Therefore, presence of TD, the evaluation of which is neither time consuming nor require sophisticated methods, should be included in pathology reports.

The value of liver-based standardized uptake value and other quantitative 18F-FDG PET-CT parameters in neoadjuvant therapy response in patients with locally advanced rectal cancer: correlation with histopathology.

AIM: We aimed to investigate the value of PET-CT in therapy response and the correlation of quantitative PET parameters with histopathologic results in patients with locally advanced rectal cancer (LARC) before and after neoadjuvant chemoradiotherapy. We also analyzed the correlation of PET-CT parameters between Ki-67 and glucose transporter 1 (GLUT1). PATIENTS AND METHODS: A total of 29 patients diagnosed with LARC who had undergone a biopsy between 2009 and 2012 were included in our study. Quantitative PET parameters [standardized uptake value (SUV)max-mean, lean body mass SUV(max-mean), tumor/liver SUV, retention index , and [INCREMENT]SUV(max)] were measured before and after therapy using PET-CT. Tumor regression grade (TRG) was evaluated according to Wheeler's classification. Patients in grade 1 were considered responders, whereas patients at grades 2 and 3 were considered nonresponders. Immunohistochemical staining with Ki-67 and GLUT1 was performed on biopsy and surgical specimens. The correlation between staining ratios and SUV was also investigated. RESULTS: SUV parameters were significantly decreased after therapy (P < 0.001). Twelve (41%) patients were at TRG1, 10 (35%) were at TRG2, and seven (24%) were at TRG3. A cutoff SUV(max) of 5.05 to discriminate between responders and nonresponders after treatment revealed a sensitivity of 57%, specificity of 73%, negative predictive value of 65%, positive predictive value of 67%, and accuracy of 66%. Using a cutoff of 3.55 for the SUV(mean) (standardized measurement of SUV with 1.2-cm-diameter region of interest) revealed a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 67, 76, 67, 76, and 72%, respectively. For a cutoff of 1.95 for the tumor SUV(mean)/liver SUV(mean), these diagnostic values after therapy were 73, 78, 82, 67, and 76%, respectively. We found a moderate correlation between liver-based SUV(max) (r = -0.35, P = 0.019) and SUV(mean )(r = -0.31, P = 0.036) with GLUT1 after therapy. Quantitative PET parameters and retention index were moderately correlated with Ki-67. CONCLUSION: PET-CT is a useful method for assessing the response to neoadjuvant chemoradiotherapy in patients with LARC. The most significant parameter for assessing treatment response using SUV parameters is the tumor/liver ratio.

Diffusion-weighted MRI and MR- volumetry--in the evaluation of tumor response after preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

PURPOSE: To determine the diagnostic performance of diffusion-weighted MRI and MR volumetry for the assessment of tumor response after preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Forty-three patients with rectal cancer who underwent preoperative CRT were prospectively examined for the study. This prospective study was approved by our institutional review board. DW- and high resolution T2-weighted imaging were performed before and after therapy. Two different diffusion gradients (b = 0 and b = 600, then separately b = 0 and b = 1000) were applied. The mean tumor volume and mean ADC values were measured before and after therapy. To evaluate the responders and nonresponders to neoadjuvant CRT, two criteria, ypT stage determined in the pathologic examination after treatment and histopathologic tumor regression grade (Ryan), were used as reference standards. The patients with a lower ypT stage than T stage in the first MRI before neoadjuvant CRT were evaluated as the responder group, while the patients with a higher or the same ypT stage relative to the first MRI T stage were evaluated as the nonresponder group. According to Ryan tumor regression grade, grade 1 was evaluated as the responders, whereas grades 2 and 3 were evaluated as the nonresponder group. The percentage ADC increase and percentage tumor volume regression were compared between the responders and nonresponders using two reference standards: T downstaging and tumor regression grade (TRG). RESULTS: Before CRT, the mean tumor ADC in the responder group was significantly lower than that in the nonresponder group (p < 0.001). At the end of CRT, the mean percentage of tumor ADC change in the responder group was significantly higher than that in the nonresponder group. The percentage tumor volume regression of the responders was significantly higher than that of the nonresponders (p = 0.001). The cut-off ADC value for discriminating between the responders and nonresponders after treatment was determined to be (b = 600) 1.03 × 10(-3)mm(2)/s and the sensitivity, 71%; specificity, 79%; accuracy, 74%; positive predictive value, 81%; negative predictive value, 68% respectively. The cut-off value for discriminating between the responders and the nonresponders after treatment was determined for b = 1000 as 1.20 × 10(-3)mm(2)/s and the sensitivity, 42%; specificity, 84%; accuracy, 60%; positive predictive value, 77%; negative predictive value, 53%. CONCLUSION: The increase in the mean tumor ADC and percentage tumor volume regression in patients with rectal cancer treated with preoperative CRT was correlated with good response. DW MR imaging is a promising non-invasive technique that can help predict and monitor early therapeutic response in patients with rectal cancer who undergo CRT.

Invasive micropapillary carcinoma of the breast: a clinicopathologic study of 103 cases of an unusual and highly aggressive variant of breast carcinoma.

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c-erb-B2 overexpression of tumors were re-evaluated. Mann-Whitney U, chi-squared, Kaplan-Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high-grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c-erbB-2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c-erb-B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log-rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c-erb-B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.

Expression of matrix metalloproteinase-2 and survivin in endometrioid and nonendometrioid endometrial cancers and clinicopathologic significance.

OBJECTIVE: To determine matrix metalloproteinase-2 and survivin expressions in endometrial cancers, their relation to clinical and histologic parameters and to investigate any difference in the expression of these markers between endometrioid and nonendometrioid cancers. METHODS: Ninety-five patients with endometrial cancer, were included. Matrix metalloproteinase-2 and survivin expressions were analyzed immunohistochemically from paraffin-embedded tissues by using specific monoclonal antibodies. RESULTS: Survivin nuclear expression was higher in endometrioid cancer as compared to nonendometrioid cancer (p=0.040), but there was no difference for cytoplasmic survivin and matrix metalloproteinase-2 expressions between type I and type II carcinomas. Survivin cytoplasmic staining was significantly lower in patients with deep myometrial invasion (p=0.038). Nuclear expression of survivin is decreased in histologic grade 3 tumors compared to grade 1 and 2 tumors (p=0.013), but there is no difference between grade 1 and 2. We did not find any statistically significant difference between survivin or matrix metalloproteinase-2 expressions and survival. CONCLUSION: Survivin and matrix metalloproteinase-2 are present in endometrioid and nonendometrioid cancers. Grade 1 and 2 tumors and carcinomas having myometrial invasion less than 50% have higher survivin expression. These results supports that, survivin may play an important role in early stage tumors and early phases of tumor development. We did not find any association between matrix metalloproteinase-2 expression and classical prognostic factors in endometrial cancer and both proteins were not associated with survival.

Effects of preoperative chemoradiotherapy on anal sphincter functions and quality of life in rectal cancer patients.

PURPOSE: Deterioration of anorectal function after long-course preoperative chemoradiotherapy combined with surgery for rectal cancer is poorly defined. We conducted a prospective study to evaluate the acute and long term effects of preoperative chemoradiotherapy on anorectal function and quality of life of the patients. METHODS: There were 26 patients in surgery group and 31 patients in preoperative chemoradiotherapy group. Anorectal function and quality of life of the patients were assessed by anorectal manometry, incontinence score, quality of life questionnaire. RESULTS: Significant lower resting pressures in both groups and lower maximal squeeze pressures in the preoperative chemoradiotherapy group were observed after postsurgical evaluations compared with the paired pretreatment ones. In the surgery group, both the Wexner continence score, FIQL score, and the rectoscopy score were comparable before and after surgery, whereas significant worsening in the Wexner score was observed in the preoperative chemoradiotherapy group postoperatively (P < 0.01). Significant reduction in anal canal resting pressures and squeeze pressures, Wexner score, and FIQL score were observed immediately after the completion of preoperative chemoradiotherapy. Significant lower maximal squeeze pressures and worsening of the Wexner scores were observed in the preoperative chemoradiotherapy group compared to the surgery group during the postoperative assessments (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: Both total mesorectal excision and preoperative chemoradiotherapy may adversely affect the anorectal function. Careful selection of the patients who will benefit from neoadjuvant therapy and identifying the patients with a high risk of developing functional problems may help to improve functional outcomes for the treatment of rectal cancer.

Depression and anxiety levels in woman under follow-up for breast cancer: relationship to coping with cancer and quality of life.

AIM: The relation of anxiety and depression levels with characteristics of coping with the disease and quality of life were evaluated in women under follow-up for breast cancer. MATERIALS AND METHODS: Patients who had presented to the breast cancer polyclinics for follow-up were evaluated. The Beck Depression and the State-Trait Anxiety inventories were used in the evaluation of depression and anxiety levels. In order to evaluate their power to cope with cancer, the patients were questioned for a social support network. EORTC QLQ-C30 and QLQ-BR23 questionnaires were applied for quality of life evaluations. RESULTS: There were 23 (19%) patients with depression; 3 (2.5%) with grade I anxiety, 94 (77%) grade II, and 23 (19%) grade III anxiety, respectively. Depression and anxiety levels were affected by the following parameters: being unaccompanied by spouse for hospital follow-ups (P < 0.0001); request to get help by a psychologist (P = 0.02); presence of a person to share their problems (P < 0.0001); and using an alternative treatment (P = 0.04). In the quality of life evaluations, difficulty in sleeping, emotional status, fatigue, and body appearance were related with both depression and anxiety (P < 0.05 for all), whereas physical function (P = 0.002), role performance (P = 0.005), cognitive condition (P < 0.0001), social position (P < 0.0001), pain (P < 0.0001), general health (P < 0.0001), treatment methods (P = 0.001), future anxiety (P < 0.0001), and arm symptoms (P = 0.001) were negatively affected in patients with depression. CONCLUSION: High depression and anxiety levels in patients under follow-up for breast cancer influence the coping with cancer and quality of life adversely.

Psychosexual and body image aspects of quality of life in Turkish breast cancer patients: a comparison of breast conserving treatment and mastectomy.

AIMS AND BACKGROUND: Assessing psychosexual and body image aspects of quality of life in Turkish breast cancer patients treated by either mastectomy or breast conserving treatment (BCT). METHODS: The study group consisted of 112 patients who had undergone all treatment at a single institution under the care of a multidisciplinary breast team. Following surgery, all patients underwent adjuvant radiotherapy with or without chemotherapy and hormone therapy. At the time of this study all patients were disease free with at least 2 years' follow-up. Twenty percent of the patients were premenopausal and 80% postmenopausal. The patients completed a questionnaire consisting of 42 questions related to their sexual relations and body image. RESULTS: Forty-one percent of sexually active patients had experienced a deterioration of sexual functioning after treatment. This was mainly due to loss of libido (80%), loss of interest in partner (54%), and sexual dissatisfaction (59%). Problems tended to develop early in the course of treatment. Decreased sexual desire was significantly more frequent in patients undergoing mastectomy versus BCT (80% vs 61%; P = 0.043) and in premenopausal versus postmenopausal patients (P = 0.024). Although 80% of patients were satisfied with their appearance as a whole, only 54% liked their naked bodies. There was no significant difference in body image scores between patients undergoing mastectomy or BCT apart from a general feeling of physical unattractiveness in mastectomy patients (3.4 vs 2.8; P = 0.03). CONCLUSIONS: Significant, similar psychosexual and body image problems occur in patients treated for breast cancer with either mastectomy or BCT. Problems arise early in the course of the disease and therefore detection and treatment of these problems should be addressed during the patients' initial assessment and at the start of treatment. These findings are similar to those reported on similar groups of treated women in American and European populations.