Immunotherapy and stereotactic body radiotherapy for older patients with non-metastatic renal cancer unfit for surgery or decline nephrectomy: practical proposal by the International Geriatric Radiotherapy Group.

The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older patients, surgery may not be an option due to the high risk of complications which may result in death. In the past renal cancer was considered to be radio-resistant, and required a higher dose of radiation leading to excessive complications secondary to damage of the normal organs surrounding the cancer. Advances in radiotherapy technique such as stereotactic body radiotherapy (SBRT) has led to the delivery of a tumoricidal dose of radiation with minimal damage to the normal tissue. Excellent local control and survival have been reported for selective patients with small tumors following SBRT. However, for patients with poor prognostic factors such as large tumor size and aggressive histology, there was a higher rate of loco-regional recurrences and distant metastases. Those tumors frequently carry program death ligand 1 (PD-L1) which makes them an ideal target for immunotherapy with check point inhibitors (CPI). Given the synergy between radiotherapy and immunotherapy, we propose an algorithm combining CPI and SBRT for older patients with non-metastatic renal cancer who are not candidates for surgical resection or decline nephrectomy.

Determinants of survival and recurrence in patients with stage I colorectal cancer.

Background: Due to the novel advanced screening methods, the number of patients diagnosed with stage I colorectal cancer (CRC) is increasing. This retrospective cohort study aimed to identify recurrence and survival risk factors of patients with stage I CRC after surgery. Materials and methods: Patients with stage I CRC were evaluated, and their demographic and clinicopathologic variables were recorded. The log-rank test assessed the association of variables with overall survival (OS), recurrence-free survival (RFS), local recurrence, and distant metastasis. Results: The median overall survival period was 51 months. The recurrence rate was 13.7%: 7.2% local and 9.3% distant recurrence. One-, two-, three-, and five-year RFS were 92%, 89%, 87%, and 83%, respectively, and OS were 96%, 93%, 90%, and 89%, respectively. Local and distant recurrence rates were higher in patients with higher tumor grades. Additionally, RFS and OS were worse in patients with higher tumor grades, and perforation was associated with worse OS. Conclusions: The determinants of survival and recurrence identified in the present study can be used to improve patient outcomes by early diagnosis and appropriate management of high-risk patients.

Immunotherapy and radiotherapy for older patients with locally advanced rectal cancer unfit for surgery or decline surgery: a practical proposal by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced rectal cancer is total neoadjuvant therapy followed by surgical resection. Current evidence suggests that selected patients may be able to delay or avoid surgery without affecting survival rates if they achieve a complete clinical response (CCR). However, for older cancer patients who are too frail for surgery or decline the surgical procedure, local recurrence may lead to a deterioration of patient quality of life. Thus, for clinicians, a treatment algorithm which is well tolerated and may improve CCR in older and frail patients with rectal cancer may improve the potential for prolonged remission and potential cure. Recently, immunotherapy with check point inhibitors (CPI) is a promising treatment in selected patients with high expression of program death ligands receptor 1 (PD- L1). Radiotherapy may enhance PD-L1 expression in rectal cancer and may improve response rate to immunotherapy. We propose an algorithm combining immunotherapy and radiotherapy for older patients with locally advanced rectal cancer who are too frail for surgery or who decline surgery.

Immunotherapy and Hypofractionated Radiotherapy in Older Patients with Locally Advanced Cutaneous Squamous-Cell Carcinoma of the Head and Neck: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

Cutaneous skin carcinoma is a disease of older patients. The prevalence of cutaneous squamous-cell carcinoma (cSCC) increases with age. The head and neck region is a frequent place of occurrence due to exposure to ultraviolet light. Surgical resection with adjuvant radiotherapy is frequently advocated for locally advanced disease to decrease the risk of loco-regional recurrence. However, older cancer patients may not be candidates for surgery due to frailty and/or increased risk of complications. Radiotherapy is usually advocated for unresectable patients. Compared to basal-cell carcinoma, locally advanced cSCC tends to recur locally and/or can metastasize, especially in patients with high-risk features such as poorly differentiated histology and perineural invasion. Thus, a new algorithm needs to be developed for older patients with locally advanced head and neck cutaneous squamous-cell carcinoma to improve their survival and conserve their quality of life. Recently, immunotherapy with checkpoint inhibitors (CPIs) has attracted much attention due to the high prevalence of program death ligand 1 (PD-L1) in cSCC. A high response rate was observed following CPI administration with acceptable toxicity. Those with residual disease may be treated with hypofractionated radiotherapy to minimize the risk of recurrence, as radiotherapy may enhance the effect of immunotherapy. We propose a protocol combining CPIs and hypofractionated radiotherapy for older patients with locally advanced cutaneous head and neck cancer who are not candidates for surgery. Prospective studies should be performed to verify this hypothesis.

Lung cancer registry and monitoring: Feasibility study and application (fars lung cancer registry project).

Background: Lung cancer (LC) is the second most common and deadliest cancer in the world. Despite the control of the progressive course of LC in developed countries, studies indicate an increase in the incidence of the disease in developing countries. We designed a stepwise approach-based surveillance system for registering LC in our region (fars lung cancer registry "FaLCaRe" Project). Materials and Methods: A questionnaire was designed and agreed upon by the steering committee using the Delphi method. Variables in nine fields were divided into three groups based on their importance: core, expanded core, and optional. The web-based data bank software was designed. The informative site about LC and team services was designed and launched for professional and community (www.falcare.org) educational purposes. Results: 545 variables in nine fields were designed (20 core variables). Primary data of 39 LC patients (24 men and 15 women) with a mean age of 62 years were analyzed. Twenty-six patients had a history of smoking. Moreover, 39% and 26% of patients had a history of hookah smoking and opium use, respectively. Adenocarcinoma was the most prevalent pathologic findings in cases. More than 80% of patients were diagnosed in stages 3 and 4 of cancer. Conclusion: FaLCaRe Project with the capabilities seen in it can be used as a model for national LC registration. With continuous valid data registry about LC, it is possible to make decisions at the national level for control and management its consequences while drawing the natural history of the LC.

The Feasibility and Safety of Induction Chemotherapy Followed by Definitive Chemoradiation in Patients with Locally Advanced Cervical Cancer: A Single-Arm Phase II Clinical Trial.

BACKGROUND: The present study aimed at investigating the feasibility and safety of induction chemotherapy followed by definitive chemoradiation (dCRT) in patients with locally advanced cervical cancer. MATERIALS AND METHODS: In this single-arm clinical trial, patients with cervical cancer (stages IB3-IVA) received a median four cycles of induction chemotherapy (paclitaxel and carboplatin, every three weeks) followed by dCRT (which consisted of the whole pelvis at the dose of 45-50 Gy along with weekly cisplatin (40 mg/m2) followed by intracavitary brachytherapy at the total dose of 80-90 Gy). Primary end point was local control at three months, which was assessed by gynecologic examination and pelvic MRI. The secondary outcome of the study was treatment-related toxicity. RESULTS: Seventy-four patients with the mean age of 51.6 ± 9.5 years were included. The most frequent (51.4%) disease stage was IIB. Complete and partial clinical responses were observed in 60.8% and 14.9% of patients, respectively. The frequency of progressive disease and stable disease were 14.9% and 9.5%, respectively. Grade II and III neutropenia (during neoadjuvant chemotherapy were 13.5% and 2.7%, respectively; these figures during chemoradiation were 29.7% and 13.5%, respectively. A treatment interruption was observed for 60.8% (45 cases) of patients during chemoradiation and 31.1% during  induction chemotherapy. DISCUSSION AND CONCLUSION: Induction chemotherapy followed by chemoradiation is feasible in patients with locally advanced cervical cancer; however, the toxicity should be managed properly to avoid delayed e treatment. More than three quarters of the patients achieved complete or partial clinical response within a three-month follow-up.

Immunotherapy and Modern Radiotherapy Technique for Older Patients with Locally Advanced Head and Neck Cancer: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced head and neck cancer is concurrent chemoradiation or postoperative irradiation with or without chemotherapy. Surgery may not be an option for older patients (70 years old or above) due to multiple co-morbidities and frailty. Additionally, the standard chemotherapy of cisplatin may not be ideal for those patients due to oto- and nephrotoxicity. Though carboplatin is a reasonable alternative for cisplatin in patients with a pre-existing hearing deficit or renal dysfunction, its efficacy may be inferior to cisplatin for head and neck cancer. In addition, concurrent chemoradiation is frequently associated with grade 3-4 mucositis and hematologic toxicity leading to poor tolerance among older cancer patients. Thus, a new algorithm needs to be developed to provide optimal local control while minimizing toxicity for this vulnerable group of patients. Recently, immunotherapy with check point inhibitors (CPI) has attracted much attention due to the high prevalence of program death-ligand 1 (PD-L1) in head and neck cancer. In patients with recurrent or metastatic head and neck cancer refractory to cisplatin-based chemotherapy, CPI has proven to be superior to conventional chemotherapy for salvage. Those with a high PD-L1 expression defined as 50% or above or a high tumor proportion score (TPS) may have an excellent response to CPI. This selected group of patients may be candidates for CPI combined with modern radiotherapy techniques, such as intensity-modulated image-guided radiotherapy (IM-IGRT), volumetric arc therapy (VMAT) or proton therapy if available, which allow for the sparing of critical structures, such as the salivary glands, oral cavity, cochlea, larynx and pharyngeal muscles, to improve the patients' quality of life. In addition, normal organs that are frequently sensitive to immunotherapy, such as the thyroid and lungs, are spared with modern radiotherapy techniques. In fit or carefully selected frail patients, a hypofractionated schedule may be considered to reduce the need for daily transportation. We propose a protocol combining CPI and modern radiotherapy techniques for older patients with locally advanced head and neck cancer who are not eligible for cisplatin-based chemotherapy and have a high TPS. Prospective studies should be performed to verify this hypothesis.

Long-Term Oncologic Outcome of Breast Cancer in Southern Iran: A Retrospective Cohort Study.

INTRODUCTION: Breast cancer remains the most frequent and lethal cancer among women worldwide. This study aimed to investigate the characteristics, prognostic factors and outcome of breast cancer patient treated and followed-up in Shiraz, southern Iran from 2000 to 2005. METHODS: In this retrospective study, 1,024 patients with breast cancer who were treated in Namazi hospital of Shiraz University of Medical Sciences between 2000 and 2005 were included. Survival analysis was performed to determine potential factors influencing disease free-and overall survival in these patients. RESULTS: Median age of the patients at diagnosis was 47 (range 19-83) years. Median follow-up for surviving patients was 68 months. The majority of patients presented at stage II (42%) and stage III (41%). Additionally, most (61%) patients had positive axillary node. The 5-, 10- and 15-year overall survival rates were 83.8%, 61.5% and 56.6% respectively. On multivariate analysis for overall survival, histologic type, Tumor stage, node stage, disease stage, M stage, hormone receptor status, adjuvant radiotherapy, and chemotherapy regimen remained independent prognostic factor for overall survival. CONCLUSION: in this study, the poor long-term oncologic outcome of the patients with breast cancer may be due to the higher rate of locally advanced disease; as well as the lack of modern systemic therapies in the study period.

Is immunotherapy at reduced dose and radiotherapy for older patients with locally advanced non-small lung cancer feasible?-a narrative review by the international geriatric radiotherapy group.

Background and Objective: The standard of care for locally advanced non-small cell lung cancer (NSCLC) is either surgery followed by adjuvant chemotherapy with or without radiotherapy or concurrent chemotherapy and radiotherapy. However, older patients (70 years old or above) with multiple co-morbidities may not be able to tolerate the combined treatment due to its toxicity. Since lung cancer prevalence increases significantly with age, a new algorithm needs to be investigated to allow curative treatment for those with locally advanced disease. Methods: A literature search of the literature was conducted through PubMed and Google Scholar using search terms such as locally advanced NSCLC, older cancer patients, immunotherapy with check point inhibitors (CPI), and image-guided radiotherapy (IGRT). Abstracts were screened, full articles fitting the article topic were reviewed, and duplicated and non-English articles were excluded. Key Content and Findings: Recently, CPI has been introduced and proven effective for selected patients with increased program death ligand 1 (PD-L1) expression (50% or above). A reduced dose for CPI (RDCPI) may be as effective as a full dose and may decrease treatment cost. New radiation technique such as IGRT may also minimize radiotherapy complication through normal lung and cardiac sparing. Conclusions: IGRT and RDCPI may be an innovative option for older patients with locally advanced NSCLC and high PD-L1 expression and needs to be investigated in future prospective studies.

Prognostic Factors of Rectal Cancer in Southern Iran.

BACKGROUND: Rectal cancer accounts for one-third of all colorectal cancer (CRC) cases. Due to physiological and anatomical differences, some researchers consider rectal cancer as a separate organ malignancy during the recent decades. However, limited studies have been conducted in this regard in Iran. Therefore, the aim of this study is to determine survival of rectal cancer and its, affecting factors in Fars province, southern Iran. METHODS: In this cohort study, we used the data of 387 patients with rectal cancer gathered by the Colorectal Research Center of Shiraz University of Medical Sciences between 2007 and 2015. The impact of 35 explanatory factors including demographic information, medical history, pathologic data, and imaging findings was evaluated using Cox regression analysis. RESULTS: Out of all patients, 111 ones (29%) died. The median follow-up period was 36 months. The patients' mean age at diagnosis was 56.72 ± 13.89 years. Their 5-year survival was 65% (95% CI: 58-69%). The results of multiple Cox regression analysis showed that sex (male/female; HR = 1.73, 95% CI: 1.15-2.67), vascular invasion (yes/no; HR = 2.40, 95% CI: 1.45-3.99), and lymph node ratio (> 0.2 vs ≤ 0.2; HR = 2.19, 95% CI: 1.41-3.40) were significantly correlated to survival. CONCLUSION: Various geographical parts of Iran show different rates regarding rectal cancer survival. A better 5-year survival rate was detected by this study for the patients with rectal cancer in Fars province, southern Iran, compared to many parts of the country. Moreover, gender, vascular invasion, and nodal status played an important role in survival of rectal cancer.

Stereotactic Body Radiotherapy and Immunotherapy for Older Patients with Oligometastases: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

The standard of care for metastatic disease is systemic therapy. A unique subset of patients with limited metastatic disease defined as distant involvement of five anatomic sites or less (oligometastases) have a better chance of remission or improved survival and may benefit from local treatments such as surgery or stereotactic body radiotherapy (SBRT). However, to prevent further spread of disease, systemic treatment such as chemotherapy, targeted therapy, and hormonal therapy may be required. Older patients (70 years old or above) or physiologically frail younger patients with multiple co-morbidities may not be able to tolerate the conventional chemotherapy due to its toxicity. In addition, those with a good performance status may not receive optimal chemotherapy due to concern about toxicity. Recently, immunotherapy with checkpoint inhibitors (CPI) has become a promising approach only in the management of program death ligand 1 (PD-L1)-positive tumors. Thus, a treatment method that elicits induction of PD-L1 production by tumor cells may allow all patients with oligometastases to benefit from immunotherapy. In vitro studies have demonstrated that high dose of radiotherapy may induce formation of PD-L1 in various tumors as a defense mechanism against inflammatory T cells. Clinical studies also corroborated those observations. Thus, SBRT, with its high precision to minimize damage to normal organs, may be a potential treatment of choice for older patients with oligometastases due to its synergy with immunotherapy. We propose a protocol combining SBRT to achieve a minimum radiobiologic equivalent dose around 59.5 Gy to all tumor sites if feasible, followed four to six weeks later by CPI for those cancer patients with oligometastases. All patients will be screened with frailty screening questionnaires to identify individuals at high risk for toxicity. The patients will be managed with an interdisciplinary team which includes oncologists, geriatricians, nurses, nutritionists, patient navigators, and social workers to manage all aspects of geriatric patient care. The use of telemedicine by the team may facilitate patient monitoring during treatment and follow-up. Preliminary data on toxicity, local control, survival, and progression-free survival may be obtained and serve as a template for future prospective studies.

Evaluation of Mucosamin Effect on Treating Radiation Induced Oral Mucositis during and after Radiotherapy amongst Patients with Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: Oral mucositis is a serious complication radiation therapy for cancer. This is a major complication during radiation therapy of the head and neck tumors in approximately all patients. Therefore, this study was conducted to evaluate the effect of Mucosamin on treatment of radiation induced oral mucositis during and after radiotherapy amongst patients with oral cavity squamous cell carcinoma. MATERIALS AND METHODS: In this prospective clinical trial, eligible patients who referred to radiation oncology department of Namazi Hospital, Shiraz, Iran from Jan 2018 till Jan 2019 were evaluated. The cases with confirmed pathologic diagnosis of squamous cell carcinoma of the oral cavity underwent 6,000 cGy radiation therapy and were randomly divided into two groups: 1- Intervention group; Mucosamin spray for 3-4 times a day (n = 40); 2 - Control group; standard medications (3 times a day) (n = 40). Oral mucositis was evaluated weekly based on RTOG scoring scale. Grade of mucositis was recorded during treatment and after radiation therapy. RESULTS: A total of 80 patients were divided in two groups of Mucosamin and control. From week 3 until the end of radiotherapy (week 6) and after radiotherapy (week 8), there was a significant difference in the severity of oral mucositis between the Mucosamin and the control groups (P <0.05). CONCLUSION: The results of this study showed that Mucosamin spray was able to significantly improved radiation-induced oral mucositis in patients with oral squamous cell carcinoma.
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Efficacy and safety of sequential neoadjuvant chemotherapy and short-course radiation therapy followed by delayed surgery in locally advanced rectal cancer: a single-arm phase II clinical trial with subgroup analysis between the older and young patients.

PURPOSE: This study was performed to investigate the efficacy and safety of short-course radiation therapy (SCRT) and sequential chemotherapy followed by delayed surgery in locally advancer rectal cancer with subgroup analysis between the older and young patients. MATERIALS AND METHODS: In this single-arm phase II clinical trial, eligible patients with locally advanced rectal cancer (T3-4 and/or N1-2) were enrolled. All the patients received a median three sequential cycles of neoadjuvant CAPEOX (capecitabine + oxaliplatin) chemotherapy. A total dose of 25 Gy in five fractions during 1 week was prescribed to the gross tumor and regional lymph nodes. Surgery was performed about 8 weeks following radiotherapy. Pathologic complete response rate (pCR) and grade 3-4 toxicity were compared between older patients (≥65 years) and younger patients (<65 years). RESULTS: Ninety-six patients with locally advanced rectal cancer were enrolled. There were 32 older patients and 64 younger patients. Overall pCR was 20.8% for all the patients. Older patients achieved similar pCR rate (18.7% vs. 21.8; p = 0.795) compared to younger patients. There was no statistically significance in terms of the tumor and the node downstaging or treatment-related toxicity between older patients and younger ones; however, the rate of sphincter-saving surgery was significantly more frequent in younger patients (73% vs. 53%; p=0.047) compared to older ones. All treatment-related toxicities were manageable and tolerable among older patients. CONCLUSION: Neoadjuvant SCRT and sequential chemotherapy followed by delayed surgery was safe and effective in older patients compared to young patients with locally advanced rectal cancer.

Determinants of delay in diagnosis and end stage at presentation among breast cancer patients in Iran: a multi-center study.

One of the reasons for high mortality of breast cancer (BC) is long delay in seeking medical care and end stage at presentation. This study was designed to measure the association between a wide range of socio-demographic and clinical factors with diagnostic delay in BC and stage at presentation among Iranian patients. From June 2017 to December 2019, 725 patients with newly diagnosed BC in Shiraz and Kermanshah were selected and information on BC diagnosis delay was obtained from the patient's medical record. Data on socio-economic status was obtained via a structured interview. Our findings suggest that 45.8% of the patients were diagnosed at a late stage (stage 3 or higher). A total of 244 (34%) patients had more than 3 months delay in diagnosis. We found a significant association between stage at diagnosis and place of residence (adjusted odds ratio (aOR rural vs. urban = 1.69, 95% CI 1.49-1.97), marital status (aOR 1.61, 95% CI 1.42-1.88), family history of BC (aOR 1.46, 95% CI 1.01-2.13), and history of benign breast disease (BBD) (aOR 1.94, 95% CI 1.39-2.72) or unaware of breast self-examination (BSE) (aOR 1.42, 95% CI 1.42-1.85), delay time (aOR 3.25, 95% CI 1.04-5.21), and left breast tumor (aOR right vs. left 2.64, 95% CI 1.88-3.71) and smoking (aOR no vs. yes 1.59, 95% CI 1.36-1.97). Also, delay in diagnosis was associated with age, family income, health insurance, place of residence, marital status, menopausal status, history of BBD, awareness of breast self-examination, type of first symptoms, tumor histology type, BMI and comorbidity (p < 0.05 for all). Factors including history of BBD, awareness of BSE, and suffering from chronic diseases were factors associated with both delay in diagnosis and end stage of disease. These mainly modifiable factors are associated with the progression of the disease.

Efficacy and Feasibility of Adding Induction Chemotherapy to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Phase II Clinical Trial.

PURPOSE: Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer. METHODS: This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3-4 and/or N1-2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45-50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary endpoints, respectively. RESULTS: The study participants included 37 males and 17 females, with a median age of 59 years (range, 20-80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent. CONCLUSION: The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.

177Lu/153Sm-Ethylenediamine Tetramethylene Phosphonic Acid Cocktail: A Novel Palliative Treatment for Patients with Bone Metastases.

Background: Production of effective, low-cost, and efficient radiopharmaceuticals is an important task and requires further research and clinical studies. In this clinical trial, safety and efficacy of 177Lu/153Sm-ethylenediamine tetramethylene phosphonic acid (EDTMP) cocktail has been evaluated for pain relief of bone metastases. Materials and Methods: Twenty-five patients with the mean age of 55.5 ± 15.8 years participated in this study. Patients received a total dose of 37 MBq/kg. Pain and performance assessments were followed using a Brief Pain Inventory form. Complete blood count and renal and liver function tests were also performed up to 12 weeks postadministration. Results: Eighteen patients (72%) demonstrated complete pain relief (relief = 100%) and approximately all patients (96%) experienced significant improvement in their quality of life. No grade IV hematological toxicity was observed during the 12-week follow-up period, and grade III toxicity was seen in 1 patient only. In addition, no abnormalities were seen in renal and liver function during the follow-up period. Conclusions: There were no considerable complications after administration of 177Lu/153Sm EDTMP; this cocktail seems to be a safe and effective treatment for bone pain palliation in patients with skeletal metastases and improves the quality of life.

Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case-control study.

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast are the most common histological subtypes of breast cancer. However, the associations and heterogeneity between histological subtypes and their risk factors are not well established. This study aimed to investigate risk factors for IDC and ILC. This case-control study included 1,009 incident breast cancer cases and 1,009 hospital controls, frequency-matched by age. Data were obtained from the patients' medical files and an interview administered via a questionnaire. Multinomial logistic regression was used and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The heterogeneity of the associations was assessed using the Wald test. Family history of breast cancer was associated with IDC (OR 2.64, 95% CI: 1.97-3.55) but not ILC (OR 0.81, 95% CI: 0.42-1.57; p for heterogeneity <0.001). Conversely, a history of miscarriage was associated with ILC (OR 1.71, 95% CI: 1.17-2.51) but not IDC (OR 1.18, 95% CI: 0.95-1.46; p for heterogeneity = 0.04). Similarly, type 2 diabetes was associated with ILC but not IDC (p for heterogeneity = 0.02). Age at first delivery and breastfeeding were significantly associated with IDC but not ILC, though p values for heterogeneity did not reach the significance level. Deliberate weight loss and age at menarche were significantly associated with ILC but not IDC (p for heterogeneity ≥0.27). Smoking, history of benign breast disease and BMI were associated with both subtypes. The present study supports the hypothesis that IDC and ILC are etiologically distinct tumours.

Insufficient lymph node assessment in gastric adenocarcinoma.

BACKGROUND: This study aimed to investigate the sufficient (≥ 16) lymph node assessment in 449 patients with gastric adenocarcinoma and literature review. METHODS: Four hundred and forty-nine patients with pathologically confirmed locoregional invasive gastric adenocarcinoma from 2004 to 2013 were included. A standard surgical resection was performed for all the patients with (n = 16) or without (n = 433) neoadjuvant treatment. RESULTS: In this study, 301 men and 148 women with a median age of 58 (range 21-88) years were included. The median total numbers of examined lymph nodes were 9 (range 0-55). Ninety-five patients (21.2%) had adequate (≥ 16) lymph node examination, and 70 patients (15.6%) had no examined lymph nodes. In univariate analysis, total or near total gastrectomy (P <  0.001), advanced node stage (P < 0.001), primary tumor size > 6 cm (P < 0.001), and the presence of perineural invasion (P = 0.039) were associated with more average number of examined lymph nodes. On multivariate analysis, node stage (P < 0.001) and type of surgery (P = 0.008) were independent predictive factors. CONCLUSION: In this study, approximately one in five patients with gastric adenocarcinoma had sufficient lymph node assessment. More studies are suggested for identifying a true inadequate lymph node dissection from insufficient lymph node assessment.

Predictive Significance of Mucinous Histology on Pathologic Complete Response Rate Following Capecitabine-Based Neoadjuvant Chemoradiation in Rectal Cancer: a Comparative Study.

INTRODUCTION: Currently, neoadjuvant fluoropyrimidine-based chemoradiation followed by surgery is considered the standard of care for locally advanced rectal cancer. The current study aimed to investigate the predictive significance of mucinous histology on the pathologic complete response rate following neoadjuvant chemoradiation in locally advanced rectal cancer and to propose potential new treatment protocol for this specific histology. MATERIAL AND METHOD: This retrospective study was conducted on 403 patients with locally advanced (clinically T3-4 and/or N1-2) rectal adenocarcinoma who had been treated at three tertiary academic hospitals between 2010 and 2015. Among those 403 patients, 46 (11%) had mucinous rectal cancer (MRC) and 358 (89%) had non-mucinous rectal cancer (NMRC). All patients underwent neoadjuvant chemoradiation with capecitabine followed by low anterior or abdominoperineal resection. RESULTS: There were 268 men and 135 women with a median age of 55 years (range, 26-82 years). Patients with MRC were younger (p = 0.002) and presented with a larger tumor size (p < 0.001) and a more advanced tumor stage (p = 0.033) compared to the ones with MNRC. In the univariate analysis, female gender (p = 0.009), distal tumor location (p = 0.035), higher tumor stage (p = 0.049), node positivity (p = 0.001), MRC histology (p = 0.017), and high pretreatment CEA level (p = 0.013) were observed to be predictive of a poor pathologic complete response. However, in the multivariate analysis, tumor stage was the single most predictive factor of response to neoadjuvant chemoradiation. CONCLUSION: Mucinous adenocarcinoma is a significant predictive factor for poor pathologic complete response to neoadjuvant capecitabine-based chemoradiation in patients with locally advanced rectal cancer. New treatment modality based on biomarkers may be considered in future prospective studies because of MRC poor prognosis. Immunotherapy combined with chemotherapy and/or radiotherapy may be an attractive option because of the tumor microsatellite instability-high status.

Effects of Different Treatment Strategies and Tumor Stage on Survival of Patients with Advanced Laryngeal Carcinoma: A 15-Year Cohort Study.

BACKGROUND: Laryngeal cancer is the second most common cancer in the head and neck. Since laryngeal cancer management is a complex process, there is still no standard strategy to treat this disease in order to increase the survival rate of the patients especially among those with advanced form of the disease. METHODS: A cohort study was undertaken to analyze factors predicting survival of the patients in advanced stage laryngeal cancer in the Southern Iran among all patients newly diagnosed with laryngeal cancer between 2000 and 2015. RESULTS: Data of a total number of 415 patients who have had been diagnosed with advanced laryngeal cancer during this period was used for analysis. The patients' 1-, 3-, 5-, and 10-year survival rates were 81%, 62%, 53%, and 38%, respectively. Multivariable Cox regression analyses indicated a significant relationship between patients' survival and age at diagnosis (P < 0.001), disease stage (P = 0.002), tumor grade (P = 0.008), positive L. node (P = 0.008), and type of treatment (P < 0.001). As expected, treatment strategy was identified as the most effective factor in survival of the patients. According to the results, patients who undergone surgical treatment experienced a longer survival than those who received other treatments. CONCLUSION: This study showed that the survival of patients depends on several factors, among which, treatment strategy is the most important. Combination of total laryngectomy plus chemoradiation provides superior local control and better survival compared to either radiotherapy or chemoradiation in patients with advanced laryngeal cancer.