Current approaches in intensification of long-course chemoradiotherapy in locally advanced rectal cancer: a review

Rectal cancer is one of the most prevalent cancers in the world. In many countries, the current standard of care is long-course chemoradiation (CRT), followed by total mesorectal excision. Some efforts have been made by intensifying radiation or chemotherapy components of the neoadjuvant therapy to further decrease the local recurrence and augment surgery’s feasibility and improve the oncological outcomes. This paper reviews recent intensified neoadjuvant interventions in locally advanced rectal cancer (LARC) in terms of efficacy and treatment-related toxicity. Many maneuvers have been made so far to improve the oncological outcomes of rectal cancer with intensified neoadjuvant long-course CRT. Some of these approaches seem compelling and deserve further study, while some have just increased the treatment-related toxicities without evident benefits. Those endeavors with greater pathological complete response than the standard of care may make us await the long-term results on survival rates and chronic treatment-related toxicity. After introduction of neoadjuvant CRT for LARC there have been many efforts to improve its outcomes. Here, this study gathered most of these efforts that intensified the neoadjuvant therapy with some being promising and some being futile.

Current approaches in intensification of long-course chemoradiotherapy in locally advanced rectal cancer: a review

Rectal cancer is one of the most prevalent cancers in the world. In many countries, the current standard of care is long-course chemoradiation (CRT), followed by total mesorectal excision. Some efforts have been made by intensifying radiation or chemotherapy components of the neoadjuvant therapy to further decrease the local recurrence and augment surgery’s feasibility and improve the oncological outcomes. This paper reviews recent intensified neoadjuvant interventions in locally advanced rectal cancer (LARC) in terms of efficacy and treatment-related toxicity. Many maneuvers have been made so far to improve the oncological outcomes of rectal cancer with intensified neoadjuvant long-course CRT. Some of these approaches seem compelling and deserve further study, while some have just increased the treatment-related toxicities without evident benefits. Those endeavors with greater pathological complete response than the standard of care may make us await the long-term results on survival rates and chronic treatment-related toxicity. After introduction of neoadjuvant CRT for LARC there have been many efforts to improve its outcomes. Here, this study gathered most of these efforts that intensified the neoadjuvant therapy with some being promising and some being futile.

Short-course versus long-course neoadjuvant chemoradiotherapy in patients with rectal cancer: preliminary results of a randomized controlled trial

Purpose@#Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. @*Materials and Methods@#Patients in group I received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/m2 from day 1–5 twice daily and oxaliplatin 50 mg/m2 on day 1 once daily). Patients in group II received a total dose of 50–50.4 Gy/25–28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/m2 twice daily. Both groups underwent delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. @*Results@#In this preliminary report on complications and pathological response, 66 patients were randomized into study groups. Mean duration of radiotherapy in the two groups was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the short-course and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment-related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group. Within one month of surgery, no significant difference was seen regarding grade ≥3 postoperative complications (p = 0.333). @*Conclusion@#For patients with rectal cancer located 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy.

Preoperative short course radiotherapy with concurrent and consolidation chemotherapies followed by delayed surgery in locally advanced rectal cancer: preliminary results

PURPOSE: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. MATERIALS AND METHODS: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. RESULTS: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. CONCLUSION: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.

Gastrointestinal tumor board: an evolving experience in Tehran Cancer Institute

Gastrointestinal [GI] cancers are a significant source of morbidity and mortality in Iran, with stomach adenocarcinoma as the most common cancer in men and the second common cancer in women. Also, some parts of Northern Iran have one of the highest incidences of esophageal cancer in the world. Multi-disciplinary organ-based joint clinics and tumor boards are a well-recognized necessity for modern treatment of cancer and are routinely utilized in developed countries, especially in major academic centres. But this concept is relatively new in developing countries, where cancer treatment centres are burdened by huge loads of patients and have to cope with a suboptimum availability of resources and facilities. Cancer Institute of Tehran University of Medical Sciences is the oldest and the only comprehensive cancer treatment centre in Iran, with a long tradition of a general tumor board for all cancers. But with the requirements of modern oncology, there has been a very welcome attention to sub-specialized organ-based tumor boards and joint clinics here in the past few years. Considering this, we started a multi-disciplinary tumor board for GI cancers in our institute in early 2010 as the first such endeavor here. We hereby review this 2-year evolving experience. The process of establishment of a GI tumor board, participations from different oncology disciplines and related specialties, the cancers presented and discussed in the 2 years of this tumor board, the general intents of treatment for the decisions made and the development of interest in this tumor board among the Tehran oncology community will be reviewed. The GI tumor board of Tehran Cancer Institute started its work in January 2010, with routine weekly sessions. A core group of 2 physicians from each surgical, radiation and medical oncology departments plus one gastroenterologist, GI pathologist and radiologist was formed, but participation from all interested physicians was encouraged. An electronic database was kept from the beginning. The number of patients presented in the tumor board increased from 4 in January 2010 to 16 in December 2011. Most patients were presented by radiation oncology department [38%] and then surgical [36%] and medical oncology [20%] departments. Physicians' participation also grew from an average of 8 each session to 12 in the same months, with a number of cancer specialists taking part from other university hospitals in Tehran. A total number of 225 patients were presented with a treatment decision made in this 2-year period. The majority of cases were colorectal [32%], stomach [23%], and esophageal [17%] cancers. The number of pancreatic [7%] and hepatobiliary [6%] cancers were much smaller. Most decisions were for a primary treatment [surgery or radiochemotherapy] and then a neoadjuvant approach. Tehran Cancer Institute's GI tumor board is one of the first multi-disciplinary organ-based tumor boards in Iran, and as such has made a successful start, establishing itself as a recognized body for clinical decisions and consultations in GI oncology. This experience is growing and evolving, with newer presentation and discussion formats and adapted guidelines for treatment of GI cancers in Iran sought

Effectiveness and complications of [153]Sm-EDTMP in palliative treatment of diffuse skeletal metastases

The aim of the present study was to evaluate the efficacy and safety profile of bone palliative therapy following administration of [153]Sm-EDTMP in patients with intractable metastatic bone pain. Sixteen patients [9 male, 7 female] aged 29-80 years [57.3 +/- 16.7 years] with severe metastasis-related bone pain resistant to analgesic medications were enrolled in the study. All patients having multiple bone metastases, positive bone scans, and estimated life expectancy of more than 2-3 months were entered the study. All patients received intravenous injection of 1.5 mCi [56 MBq]/kg of [153]Sm-EDTMP. Four subscales for the intensity of pain were recorded: one as the present pain score [PPS] and the other three as maximum pain score [Max PS], minimum pain score [Min PS] and average pain score [APS] over the last 24 hours. Also the mean value of these 4 subscales was calculated as the mean total pain score [MTPS]. The pain mental interference [PMI] was also assessed in 9 separate. Seven patients with breast cancer [43.75%], seven with prostate cancer [43.75%], one with papillary thyroid carcinoma [6.25%] and one with malignant paraganglioma [6.25%] were included in the study. A significant response to therapy, i.e. 2-point reduction in pain score and/or remarkable reduction [>/=25%] in the equivalent narcotic dose, was observed in 11 out of 16 patients [68.7%] by the 2nd week and in 12 patients [75%] by the 8[th] week. Regarding the palliative response to treatment and equivalent narcotic dose reduction, no significant difference between two major types of underlying malignancies [breast and prostate cancer] was found. There was no significant difference regarding response to therapy between two genders and among different age groups. The severity of bone marrow suppression was graded

[Neoadjuvant chemotherapy of epirobicin, oxaliplatin, capecitabine regimen in patients with advanced gastric cancer: a two year study]

Gastric cancer is an important health problem across the world. Chemotherapy in combination with local treatment is the standard treatment for locally advanced gastroesophageal junction [EGJ] cancers. The purpose of this study was to evaluate response and tolerability to neoadjuvant regimen combining epirobicin, oxaliplatin and capecitabin [EOX] in locoregionally advanced gastric cancer. We recruited 28 patients with histologically confirmed advanced gastric or EGJ adenocarcinoma in this study performed in the Cancer Institute of Imam Khomeini Hospital in Tehran, Iran in 2010-2011. Staging workup included chest and abdominal computed tomography [CT] scans, upper gastrointestinal endoscopy, endoscopic ultrasonography [EUS], measurement of carcinoembryonic antigen [CEA], complete blood cell count [CBC], and liver and renal function tests. After three treatment cycles with EOX regimen, we evaluated response to the neoadjuvant chemotherapy by performing endoscopic ultrasonography [EUS] and chest and abdominal CT scans. The mean age of the patients was 56.64+/-11.08 years [ranging from 37 to 78 years]. Most patients were classified as having stage III [98.8%] cancer before chemotherapy while most were classified as stage II [57.14%] after the treatment. Only 28.5% of tumors were resectable before chemotherapy, but 82.1% of them were resectable upon the treatment. 75% of tumors were downstaged after chemotherapy. Regarding the acceptable response and downstaging of tumors and low toxicity of EOX regimen in locoregionally advanced gastric cancer, evaluation of this regimen as a neoadjuvant chemotherapy in larger phase III clinical trials in Iranian patients would be both necessary and logical

Chemoradiation in nasopharyngeal carcinoma: a 6-year experience in Tehran cancer institute

To determine the addition of value of neoadjuvant, concurrent and adjuvant chemotherapy to radiation in the treatment of nasopharyngeal carcinoma with regard to the overall survival [OS] and disease free survival [DPS] within a six year period in Tehran cancer institute. Files of all patients with nasopharyngeal carcinoma treated by radiotherapy with or without concurrent chemotherapy in a curative setting in Tehran cancer institute during the period of 1999-2005 were retrospectively reviewed. A total of 103 patients with nasopharyngeal carcinoma had been treated during the study period with radiotherapy or chemoradiotherapy in our institute. There were 29 [28.2%] females and 74 [71.8%] males. The median age at the time of radiotherapy was 47 years old [range 9-75 years]. The patients were followed 2 to 76 months with a median follow-up of 14 months. Time of first recurrence after treatment was 3-44 months with a median of 10 months. Survival in 2 groups of patients treated with radiotherapy alone or chemoradiation did not have a significant difference [P>0.1]. Two-year survival in patients treated with or without adjuvant chemotherapy and had local recurrence after treatment did not have significant difference [P>0.1]. Two-year survival in patients with or without local recurrence after treatment did not have significant difference [P>0.1]. A beneficial effect or a survival benefit of adjuvant/neoadjuvant chemotherapy and concurrent chemoradiation was not observed in Iranian patients

Evaluation of human breast adenocarcinoma [MCF-7] cells proliferation in co-culture with human adipocytes in three dimensional collagen gel matrix: norepinephrine as a lipolytic factor

Norepinephrine plays a trophic role in the control of cell replication and differentiation in target cells that express adrenergic receptors. In this study, we have tested the influence of infraphysiological, physiological and supraphysiological concentrations [0.0001 nM, 1 nM, 10000 nM] of human norepinephrine on the proliferation of breast cancer cells [human breast adenocarcinoma [MCF-7]] in co-culture with human adipocytes in three-dimensional collagen gel matrix culture. Cell proliferation and lipolysis rate were measured by 3-[4, 5-dimethylthiazolyl]-2, 5-diphenyl-tetrazolium bromide [MTT] and Oil red O colorimetric assay in second, 7[th] and 14[th] days of culture experiments. Our results showed a direct correlation between lipolysis rate of adipocytes and proliferation rate of MCF-7 cells. Both physiological and supraphysiological concentrations of human norepinephrine significantly [P<0.05] increased the proliferation of MCF-7 cells synchronously with progress of adipocyte lipolysis. The proliferations of MCF-7 cells were significantly decreased after conversion of adipocytes to fibroblast-like cells by supraphysiological concentration of norepinephrine. There was no statistical difference in lipolysis of adipocytes and proliferation of MCF-7 cells in response to infraphysiological concentration of norepinephrine. These findings indicated that norepinephrine stimulated the proliferation of MCF-7 cells in co-culture with human adipocytes as a lipolytic factor and that norepinephrine effect was suppressed by conversion of adipocytes to fibroblast-like cells, suggesting adipocytes as another target for prevention and therapy of breast cancer

Quantitative assessment of salivary gland function by radioisotopic scanning in a randomized trial of pilocarpine for prevention of radiation induced xerostomia

Radioisotope scanning is the best method for objective assessment of salivary gland function. Thus, it was used in a randomized trial of concomitant pilocarpine for assessment of radiation-induced xerostomia, in addition to subjective evaluation by an approved questionnaire and objective standard xerostomia grading. Patients randomized in placebo-controlled trial of pilocarpine concurrent with irradiation for prevention of radiation-induced xerostomia were evaluated by salivary gland scintigraphy immediately before and 6 months after the end of head and neck radiotherapy. Salivary gland function was measured by ejection fraction [EF] of Technetium-99m pertechnetate. The mean values for pre and post-radiotherapy scans were calculated and compared. Also post-radiotherapy scan findings in the two groups of pilocarpine and placebo were compared using the student's t-test. In addition, comparison was made between the scan results and the subjective findings and objective gradings. Twenty patients underwent the pre-radiotherapy salivary scintigraphy, and also 20 post-radiotherapy scans were performed. Mean parotid EF was 60.85% in the pre-radiotherapy and 9.08% in the post-radiotherapy scans [P<0.01]. The means for submandibular glands in the pre and post-radiotherapy scans were 41% and 11.2%, respectively [P<0.01]. Also the mean EF was 14.5% in the pilocarpine group and 3.65 in the placebo group for parotid glands [P=0.07] and 18.3% and 4.1% respectively for submandibular glands [P<0.05]. The salivary scans confirmed the subjective and objective xerostomia findings. Salivary gland scintigraphy is a valuable method for evaluation of xerostomia after head and neck radiotherapy, quantitatively demonstrating the protective effect of pilocarpine compared to placebo on salivary glands

eight-year study of the thyroid cancer cases treated in Tehran cancer institute's radiation-oncology department

A retrospective study was undertaken to examine the thyroid cancer cases referred for external radiotherapy to our department during the period of 1991-99. Within this period, a total of 33 patients had been treated by irradiation for thyroid cancer or its metastases and these cases were evaluated for age, sex, pathology and type of surgery. The reason of patients' referral for external radiotherapy [The main aim of our study] was tumor extensive infiltration of the neck soft tissue and/or lymph nodes in 21 cases [64%], and tumor metastasis in 12 cases [36%]. Twenty-one patients came back for follow-up, who were all symptom-free 12-18 months after irradiation