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.

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.

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.

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.

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.

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.

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.

Paclitaxel-carboplatin induced radiation recall colitis.

Some chemotherapeutic agents can "recall" the irradiated volumes by skin or pulmonary reactions in cancer patients who previously received radiation therapy. We report a recall colitis following the administration of paclitaxel-containing regimen in a patient who had been irradiated for a carcinoma of the uterine cervix. A 63-year-old woman underwent a Wertheim operation because of uterine cervix carcinoma. After 8 years of follow-up, a local recurrence was observed and she received curative external radiotherapy (45 Gy) to the pelvis. No significant adverse events were observed during the radiotherapy. Approximately one year later, she was hospitalized because of metastatic disease with multiple pulmonary nodules, and a chemotherapy regimen consisting of paclitaxel and carboplatin was administered. The day after the administration of chemotherapy the patient had diarrhea and rectal bleeding. Histological examination of the biopsy taken from rectal hyperemic lesions showed a radiation colitis. The symptoms reappeared after the administration of each course of chemotherapy and continued until the death of the patient despite the interruption of the chemotherapy. In conclusion, the probability of recall phenomena should be kept in mind in patients who received previously with pelvic radiotherapy and treated later with cytotoxic chemotherapy.