A comparison of timely completion of hypofractionated and traditional adjuvant radiation therapy in early-stage breast cancer: Evidence of impact on reducing racial and socioeconomic disparities.

BACKGROUND: Timely completion of adjuvant radiation after breast conservation therapy is associated with decreased mortality and increased disease-free survival. Few data exist comparing timely completion between hypofractionated radiation and traditional radiation at a national level or across racial and socioeconomic cohorts. METHODS: A retrospective review of the National Cancer Database (2012-2016) on patients undergoing breast conservation therapy for early-stage breast cancer, specifically T1 or T2, N0, M0 patients, was performed. Multivariable logistic regression models were used to compare timely completion of hypofractionated radiation (within 5 weeks of initiation) and traditional radiation (within 7 weeks) across patient, tumor, and facility characteristics. RESULTS: In total, 210,816 patients met criteria, with 59.4% receiving traditional radiation (n = 125,140) and 40.6% receiving hypofractionated radiation (n = 85,676). Overall, 82.8% of patients achieved timely completion of radiation. Among hypofractionated radiation patients, 94.5% of patients achieved timely completion, whereas only 74.8% of traditional radiation patients achieved timely completion (P < .0001). Regarding race/ethnicity, all groups benefited substantially in timely completion of hypofractionated radiation over traditional radiation. However, both treatment cohorts demonstrated that Black (odds ratio (hypofractionated radiation) = 0.842, odds ratio (traditional radiation) = 0.821) and Hispanic (odds ratio (hypofractionated radiation) = 0.917, odds ratio (traditional radiation) = 0.907) patients had lower odds of timely completion compared to White patients (P < .0001). Lower high school graduation rate, median income for patients' ZIP code, and Medicaid were also associated with lower odds of timely completion for both hypofractionated radiation and traditional radiation (both P < .0001). CONCLUSION: Timely completion of radiation therapy in breast conservation therapy is greater for patients receiving hypofractionated radiation than traditional radiation across racial and socioeconomic cohorts. Disparities in timely completion were substantially reduced with hypofractionated radiation utilization. However, there are treatment disparities across racial and socioeconomic cohorts that persist in both treatment groups.

A Pilot Study of Hepatic Irradiation with Yttrium-90 Microspheres Followed by Immunotherapy with Ipilimumab and Nivolumab for Metastatic Uveal Melanoma.

Background: Liver metastases from uveal melanoma carry a very poor prognosis. Hepatic artery infusions with Yttrium-90 (90Y) resin microspheres have some activity in this disease, and radiation and immunotherapy may be synergistic. The primary objective of this study was to determine the safety and tolerability of sequential 90Y resin microspheres and immunotherapy with ipilimumab and nivolumab in metastatic uveal melanoma. Materials and Methods: Twenty-six patients with uveal melanoma with hepatic metastases were entered into a pilot study. Treatment consisted of two infusions of 90Y resin microspheres, one to each lobe of the liver, followed in 2-4 weeks by immunotherapy with ipilimumab and nivolumab every 3 weeks for four doses, then maintenance immunotherapy with nivolumab alone. Results: Initial dosing of both 90Y and immunotherapy resulted in excessive toxicity. With decreasing the dosage of 90Y to limit the normal liver dose to 35Gy and lowering the ipilimumab dose to 1 mg/kg, the toxicity was tolerable, with no apparent change in efficacy. There was one complete and four confirmed partial responses, for an objective response rate of 20% and a disease control rate of 68%. The median progression-free survival was 5.5 months (95% confidence interval [CI]: 1.3-9.7 months), with a median overall survival of 15 months (95% CI: 9.7-20.1 months). Conclusions: With dose reductions, sequential therapy with 90Y and immunotherapy with ipilimumab and nivolumab is safe and tolerable, and has activity in metastatic uveal melanoma. These results justify a controlled trial to demonstrate whether 90Y resin microspheres add to the utility of combination immunotherapy in this disease. Clinical Trial Registration number: NCT02913417.

Onco-metabolism: defining the prognostic significance of obesity and diabetes in women with brain metastases from breast cancer.

PURPOSE: Metabolic dysregulation has been implicated as a molecular driver of breast cancer in preclinical studies, especially with respect to metastases. We hypothesized that abnormalities in patient metabolism, such as obesity and diabetes, may drive outcomes in breast cancer patients with brain metastases. METHODS: We retrospectively identified 84 consecutive patients with brain metastases from breast cancer treated with intracranial radiation therapy. Radiation was delivered as whole-brain radiation to a median dose of 3000 cGy or stereotactic radiosurgery to a median dose of 2100 cGy. Kaplan Meier curves were generated for overall survival (OS) data and Mantel-Cox regression was performed to detect differences in groups. RESULTS: At analysis, 81 survival events had occurred and the median OS for the entire cohort was 21.7 months. Despite similar modified graded prognostic assessments, resection rates, and receptor status, BMI ≥ 25 kg/m2 (n = 45) was associated with decreased median OS (13.7 vs. 30.6 months; p < 0.001) and median intracranial progression-free survival (PFS) (7.4 vs. 10.9 months; p = 0.04) compared to patients with BMI < 25 kg/m2 (n = 39). Similar trends were observed among all three types of breast cancer. Patients with diabetes (n = 17) had decreased median OS (11.8 vs. 26.2 months; p < 0.001) and median intracranial PFS (4.5 vs. 10.3 months; p = 0.001) compared to non-diabetics (n = 67). On multivariate analysis, both BMI ≥ 25 kg/m2 [HR 2.35 (1.39-3.98); p = 0.002] and diabetes [HR 2.77 (1.454-5.274); p = 0.002] were associated with increased mortality. CONCLUSIONS: Elevated BMI or diabetes may negatively impact both overall survival and local control in patients with brain metastases from breast cancer, highlighting the importance of the translational development of therapeutic metabolic interventions. Given its prognostic significance, BMI should be used as a stratification in future clinical trial design in this patient population.

Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.

OBJECTIVES: Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. METHODS: Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. RESULTS: Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. CONCLUSIONS: Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

Increasing faculty participation in resident education and providing cost-effective self-assessment module credit to faculty through resident-generated didactics.

PURPOSE/OBJECTIVE(S): Board certified radiation oncologists and medical physicists are required to earn self-assessment module (SAM) continuing medical education (CME) credit, which may require travel costs or usage fees. Data indicate that faculty participation in resident teaching activities is beneficial to resident education. Our hypothesis was that providing the opportunity to earn SAM credit in resident didactics would increase faculty participation in and improve resident education. METHODS AND MATERIALS: SAM applications, comprising CME certified category 1 resident didactic lectures and faculty-generated questions with respective answers, rationales, and references, were submitted to the American Board of Radiology for formal review. Surveys were distributed to assess main academic campus physician, affiliate campus physician, physicist, and radiation oncology resident impressions regarding the quality of the lectures. Survey responses were designed in Likert-scale format. Sign-test was performed with P < .05 considered statistically different from neutral. RESULTS: First submission SAM approval was obtained for 9 of 9 lectures to date. A total of 52 SAM credits have been awarded to 4 physicists and 7 attending physicians. Main academic campus physician and affiliate campus physician attendance increased from 20% and 0%, respectively, over the 12 months preceding CME/SAM lectures, to 55.6% and 20%, respectively. Survey results indicated that the change to SAM lectures increased the quality of resident lectures (P = .001), attending physician participation in resident education (P < .0001), physicist involvement in medical resident education (P = .0006), and faculty motivation to attend resident didactics (P = .004). Residents reported an increased amount of time required to prepare lectures (P = .008). CONCLUSIONS: We are the first department, to our knowledge, to offer SAM credit to clinical faculty for participation in resident-generated didactics. Offering SAM credit at resident lectures is a cost-effective alternative to purchasing SAM resources, increases faculty attendance, and may improve the quality of radiation oncology resident education.

Yttrium-90 Microsphere Brachytherapy for Liver Metastases From Uveal Melanoma: Clinical Outcomes and the Predictive Value of Fluorodeoxyglucose Positron Emission Tomography.

OBJECTIVES: To report outcomes after yttrium-90 microsphere brachytherapy for unresectable liver metastases from uveal melanoma and to evaluate factors predictive for overall survival (OS) and hepatic progression-free survival (PFS). METHODS: A total of 71 patients were consecutively treated with microsphere brachytherapy for unresectable liver metastases from uveal melanoma between 2007 and 2012. Clinical, radiographic, and positron emission tomography-derived, functional tumor parameters were evaluated by log-rank test in univariate analysis and backwards stepwise multivariate Cox proportional hazards regression. OS and hepatic PFS were estimated by Kaplan-Meier analysis. RESULTS: A total of 134 procedures were performed in 71 patients with a median age of 63 years (range, 23 to 91 y). Fifty-eight patients (82%) received microsphere brachytherapy as a salvage therapy. Median hepatic PFS and OS after microsphere brachytherapy were 5.9 months (range, 1.3 to 19.1 mo) and 12.3 months (range, 1.9 to 49.3 mo), respectively. Median OS times after diagnosis of liver metastases was 23.9 months (range, 6.2 to 69.0 mo). In univariate analysis, female sex, pretreatment metabolic tumor volume, and total glycolic activity (TGA) were significantly correlated with hepatic PFS and OS. In multivariate analysis, female sex and TGA retained significance as independent predictors of hepatic PFS and OS. A low pretreatment TGA (<225 g) was associated with a significantly longer median OS than was a TGA≥225 g (17.2 vs. 9.7 mo, P=0.01). CONCLUSIONS: Yttrium-90 microsphere brachytherapy provided favorable survival times in patients with unresectable liver metastases from uveal melanoma. Metabolic tumor volume and TGA are predictive functional tumor parameters, which may aid patient selection and risk stratification.

Pulpectomies in primary mandibular molars: a comparison of outcomes using three root filling materials.

AIM: To evaluate the outcome of root canal treatment in primary teeth using three root canal filling materials - RC Fill, Vitapex and Pulpdent root canal sealer. METHODOLOGY: The study was a single-centre, double-blind, randomized controlled trial carried out on 129 primary mandibular molars with necrotic pulps or irreversible pulpitis in 4- to 9-year-old children. Participants were selected based on specific inclusion and exclusion criteria and were randomly allocated into 3 groups: Group I - RC Fill [zinc oxide-eugenol (ZOE) with iodoform]; Group II - Vitapex (calcium hydroxide with iodoform); and Group III - Pulpdent root canal sealer (ZOE). The outcome measures were evaluated both clinically and radiographically at 6, 12 and 30 months according to modified American Association of Endodontists (AAE) criteria. The radiographic outcomes were assessed by two blinded and calibrated evaluators. Pearson's chi-square analysis was performed for both intention-to-treat (ITT) and per-protocol population. RESULT: The success rates of RC Fill, Vitapex and Pulpdent were 94%, 90% and 97%, respectively, at 30 months and the differences were not significant (P = 0.137). CONCLUSION: All three materials were found to be equally effective root filling materials for primary molars with necrotic pulps and irreversible pulpitis at 30 months. However, long-term follow-up until the eruption of the permanent successor teeth is needed for more definitive assessments.

Modeled risk of ischemic heart disease following left breast irradiation with deep inspiration breath hold.

PURPOSE: Deep inspiration breath hold (DIBH) dramatically reduces radiation dose to the heart during radiation therapy (RT) for left-sided breast cancer, but the subsequent risk of radiation-related ischemic heart disease (IHD) is unknown. Our primary objective was to quantify the risk of IHD following RT with DIBH using modeled risk estimates (MRE). METHODS AND MATERIALS: Patients with stage 0-III left-sided breast cancer who received RT with DIBH were retrospectively studied. Computed tomography simulations were performed with DIBH and during free breathing (FB) for comparison of dosimetry. Patients were classified as high risk, at risk, or at optimal risk for IHD and baseline risk estimates for IHD were obtained from historic controls. The excess relative risk of IHD because of left breast RT was calculated using patient-specific dosimetry and an existing dose-effect model. MRE were determined from the sum of baseline risk estimates and excess risk. RESULTS: Between 2002 and 2011, 111 patients were treated using DIBH and 104 were available for analysis. MRE for 10-year risk of IHD with DIBH and FB were 3.25% (interquartile range [IQR], 1.20-3.44) and 3.64% (IQR, 1.43-3.81) (P < .0001), respectively. MRE for lifetime risk of IHD with DIBH and FB were 9.71% (IQR, 1.98-16.62) and 10.28% (IQR, 2.05-16.97) (P < .0001), respectively. MRE were significantly reduced by use of DIBH in all risk groups. The largest absolute risk reduction resulting from the DIBH technique was observed in patients at high risk for IHD. The median relative risk reduction in MRE resulting from DIBH was 11.4% (range, 0-32.0) and 6.4% (range, 0-23.4) at 10 years and throughout the patients' lifetime, respectively. After a median follow-up of 7.0 years (range, 1.3-11.2), the estimated 10-year freedom from IHD was 99.0% (95% confidence interval 93.4-99.8). CONCLUSIONS: RT with DIBH may provide breast cancer survivors a clinically significant reduction in the risk of IHD.

Active Breathing Coordinator reduces radiation dose to the heart and preserves local control in patients with left breast cancer: report of a prospective trial.

PURPOSE: Incidental radiation dose to the heart and lung during breast radiation therapy (RT) has been associated with an increased risk of cardiopulmonary morbidity. We conducted a prospective trial to determine if RT with the Active Breathing Coordinator (ABC) can reduce the mean heart dose (MHD) by ≥20% and dose to the lung. METHODS AND MATERIALS: Patients with stages 0-III left breast cancer (LBC) were enrolled and underwent simulation with both free breathing (FB) and ABC for comparison of dosimetry. ABC was used during the patient's RT course if the MHD was reduced by ≥5%. The median prescription dose was 50.4 Gy plus a boost in 77 patients (90%). The primary endpoint was the magnitude of MHD reduction when comparing ABC to FB. Secondary endpoints included dose reduction to the heart and lung, procedural success rate, and adverse events. RESULTS: A total of 112 patients with LBC were enrolled from 2002 to 2011 and 86 eligible patients underwent both FB and ABC simulation. Ultimately, 81 patients received RT using ABC, corresponding to 72% procedural success. The primary endpoint was achieved as use of ABC reduced MHD by 20% or greater in 88% of patients (P < .0001). The median values for absolute and relative reduction in MHD were 1.7 Gy and 62%, respectively. RT with ABC provided a statistically significant dose reduction to the left lung. After a median follow up of 81 months, 8-year estimates of locoregional relapse, disease-free, and overall survival were 7%, 90%, and 96%, respectively. CONCLUSIONS: ABC was well tolerated and significantly reduced MHD while preserving local control. Use of the ABC device during RT should be considered to reduce the risk of ischemic heart disease in populations at risk.

Radiation therapy use and outcomes among older women with ER-positive and ER-negative stage I breast cancer.

OBJECTIVE: We performed a population-based analysis to evaluate changes in patterns of radiation therapy (RT) usage after breast-conserving surgery (BCS) and outcomes among women aged 70 years or older with stage I breast cancer. METHODS: We used the Surveillance, Epidemiology and End Results database to identify 33,350 women aged 70 years or older diagnosed from 1990 to 2008 with stage I invasive ductal breast cancer treated with BCS. Patients were stratified by estrogen receptor (ER) status, and classified by RT modality: external beam RT, brachytherapy (BT), other, or none. Usage frequency for each modality was tabulated from 2000 to 2008 subset. Predictors of omission of RT and use of BT were determined by multiple logistic regression. Cox proportional hazard models were created to evaluate the effect of RT usage on breast cancer-specific mortality. RESULTS: The use of external beam RT decreased during 2000 to 2008. Omission of RT after BCS increased in patients with ER-positive tumors, whereas use of BT increased for both ER-positive and ER-negative tumors. Predictors for the use of BT were later year of diagnosis, metropolitan residence, and highest income quartile. Omission of use of any RT was associated with increased risk of breast cancer-specific mortality among both ER-positive and ER-negative cancers, with greater effect in ER-negative women. CONCLUSIONS: Among older women with stage I breast cancer treated with BCS, use of any RT has been omitted more frequently and BT utilized more often. Further studies are necessary to evaluate potential under-utilization of RT, particularly among women with ER-negative tumors.

Conditional survival probabilities for patients with resected pancreatic adenocarcinoma.

BACKGROUND: The purpose of this study is to evaluate conditional survival probabilities for patients with resected pancreatic adenocarcinoma (PC). METHODS: Patients with resected PC from 1998 to 2008 were identified from the Surveillance, Epidemiology and End Results Database. Data on patient, tumor, and treatment characteristics were extracted. Overall survival (OS) rates were calculated using the Kaplan-Meier method. A multivariable analysis at different time points from survival was performed to determine independent prognostic factors associated with all-cause mortality hazard ratios using Cox proportional hazards models. RESULTS: A total of 4883 patients with resected PC were identified. The 1-, 3-, and 5-year survival estimates for patients at diagnosis were 67%, 29%, and 21%, respectively. The probability of surviving an additional 1-, 3-, or 5-year conditional upon already surviving 5 years after diagnosis were 89%, 76%, and 71%, respectively. Prognostic factors significantly correlated with improved OS at the time of diagnosis on multivariable analysis include: earlier stage, younger age, later year of diagnosis, white ethnicity, female sex, and residence in a high income district (P<0.05). Among those already surviving 3 years after diagnosis, younger age was the only prognostic factor statistically significantly correlated with improved OS (P<0.05). CONCLUSIONS: Conditional survival estimates provide additional prognostic information that may be used to counsel PC patients on how their prognosis may change over time. Further research using prospectively collected data is warranted to help determine recommended follow-up intervals and benchmarks for future clinical trials.

Radiation therapy for locally recurrent breast cancer.

Approximately one-third of all breast cancer patients experience local recurrence of their tumor after initial treatment. As initial treatment often employs the use of radiation therapy (RT), the standard of care for local breast cancer recurrence after initial breast conserving therapy has traditionally been surgical intervention with mastectomy. However, recent attempts to preserve the intact breast after recurrence with local excision have revealed a potential need for RT in addition to repeat breast conserving surgery as rates of local failure with resection alone remain high. Additionally, local recurrence following initial mastectomy and chest wall RT can be treated with reirradiation to increase local control. Repeating RT, however, in a previously irradiated area, is a complex treatment strategy, as the clinician must carefully balance maximizing treatment effectiveness while minimizing treatment-related toxicity. As a result, physicians have been hesitant to treat recurrent disease with repeat RT with limited data. Results from the current literature are promising and current clinical trials are underway to explore reirradiation modalities which will provide additional information on treatment-related toxicity and outcomes. This paper will review the current literature on repeat radiation therapy for locally recurrent breast cancer.

Weekly paclitaxel, gemcitabine, and external irradiation followed by randomized farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) multi-institutional Phase II study 98-12, evaluating paclitaxel and concurrent radiation (RT) for locally advanced pancreatic cancer, demonstrated a median survival of 11.3 months and a 1-year survival of 43%. The purpose of the randomized Phase II study by RTOG 0020 was to evaluate the addition of weekly low- dose gemcitabine with concurrent paclitaxel/RT and to evaluate the efficacy and safety of the farnesyl transferase inhibitor R115777 following chemoradiation. PATIENTS AND METHODS: Patients with unresectable, nonmetastatic adenocarcinoma of the pancreas were eligible. Patients in Arm 1 received gemcitabine, 75 mg/m(2)/week, and paclitaxel, 40 mg/m(2)/week, for 6 weeks, with 50.4 Gy radiation (CXRT). Patients in Arm 2 received an identical chemoradiation regimen but then received maintenance R115777, 300 mg twice a day for 21 days every 28 days (CXRT+R115777), until disease progression or unacceptable toxicity. RESULTS: One hundred ninety-five patients were entered into this study, and 184 were analyzable. Grade 4 nonhematologic toxicities occurred in less than 5% of CXRT patients. The most common grade 3/4 toxicity from R115777 was myelosuppression; however, grade 3/4 hepatic, metabolic, musculoskeletal, and neurologic toxicities were also reported. The median survival time was 11.5 months and 8.9 months for the CXRT and CXRT+R115777 arms, respectively. CONCLUSIONS: The CXRT arm achieved a median survival of almost 1-year, supporting chemoradiation as an important therapeutic modality for locally advanced pancreatic cancer. Maintenance R115777 is not effective and is associated with a broad range of toxicities. These findings provide clinical evidence that inhibition of farnesylation affects many metabolic pathways, underscoring the challenge of developing an effective K-ras inhibitor.

Head and neck carcinoma in the United States: first comprehensive report of the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN).

BACKGROUND: Detailed information about how patients with head and neck carcinoma (HNC) are treated across practice settings does not exist. The authors conducted a prospective, observational study to examine the patterns of care for a series of patients with newly diagnosed HNC in the United States and to test 2 hypotheses: 1) There is no difference in the pattern of care between community and academic settings; and 2) the results of major randomized clinical trials will change the pattern of care in both practice settings within 1 year of publication in peer-reviewed journals. METHODS: Patients aged ≥ 18 years were enrolled in the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN) after providing written informed consent if they had a confirmed diagnosis of new HNC and were scheduled to receive treatment other than surgery alone. RESULTS: Between 2005 and 2010, 100 centers enrolled 4243 patients, including 2612 patients (62%) from academic investigators and 1631 patients (38%) from community centers. Initial treatments were radiation with concurrent chemotherapy (30%) or cetuximab (9%), adjuvant radiotherapy (21%), induction chemotherapy (16%), and other (24%). Intensity modulated radiation therapy was the dominant radiation technique (84%). Single-agent cisplatin was prescribed in nearly half of patients and more often in academic centers (53% vs 43% of patients; P < .0001). Single-agent cetuximab was the next most common drug used (19%) and was prescribed more frequently in community settings (24% vs 17%; P = .0001). The data rejected the 2 prospective hypotheses. CONCLUSIONS: LORHAN documented differences in patient characteristics and treatments between community and academic settings for a large series of patients in the United States.

Regeneration potential of pulp-dentin complex: Systematic review.

AIM: The aim is to review and discuss the strategies available for the regeneration of tooth tissues based on principles of tissue engineering. BACKGROUND: Tissue engineering is a multidisciplinary approach that aims to regenerate functional tooth-tissue structure based on the interplay of three basic key elements: Stem cells, morphogens and scaffolds. A number of recent clinical case reports have revealed the possibilities that many teeth that traditionally would be treated byapexification may be treated by apexogenesis. MATERIALS AND METHODS: Electronic and hand search of scientific papers were carried out on the Entrez Pubmed, and the Cochrane Central Register of Controlled Trials databases using specific keywords. Specific inclusion and exclusion criteria were predetermined. The search yielded 1619 papers; out of which 65 were identified as conforming to the predetermined inclusion criteria and the remaining 1554 were excluded. Out of 65 papers, 34 papers were excluded again as different key words led to the same publications. Only 31 papers were selected, out of which 27 full-text papers were found and 4 papers were included based on only the abstracts. These 31 papers formed the basis of this review. The data were extracted from the selected studies. The data were synthesized by pooling the extracted data. CONCLUSION: The field of tissue engineering has recently shown promising results and is a good prospect in dentistry for the development of the ideal restorations to replace the lost tooth structure.

Phase I trial using the proteasome inhibitor bortezomib and concurrent chemoradiotherapy for head-and-neck malignancies.

PURPOSE: Advanced head-and-neck cancer (HNC) remains a difficult disease to cure. Proteasome inhibitors such as bortezomib have the potential to improve survival over chemoradiotherapy alone. This Phase I dose-escalation study examined the potential of bortezomib in combination with cisplatin chemotherapy and concurrent radiation in the treatment of locally advanced and recurrent HNC. METHODS AND MATERIALS: Eligible patients received cisplatin once weekly at 30 mg/m(2) per week and bortezomib along with concurrent radiation. Bortezomib was given on Days 1, 4, 8, and 11 every 3 weeks, with an initial starting dose of 0.7 mg/m(2) and escalation levels of 1.0 and 1.3 mg/m(2). Dose escalation was performed only after assessment to rule out any dose-limiting toxicity. RESULTS: We enrolled 27 patients with HNC, including 17 patients with recurrent disease who had received prior irradiation. Patients received bortezomib dose levels of 0.7 mg/m(2) (7 patients), 1.0 mg/m(2) (10 patients), and 1.3 mg/m(2) (10 patients). No Grade 5 toxicities, 3 Grade 4 toxicities (all hematologic and considered dose-limiting toxicities), and 39 Grade 3 toxicities (in 20 patients) were observed. With a median follow-up of 7.4 months, the overall median survival was 24.7 months (48.4 months for advanced HNC patients and 15.4 months for recurrent HNC patients). CONCLUSION: Bortezomib in combination with radiation therapy and cisplatin chemotherapy is safe in the treatment of HNC with a bortezomib maximum tolerated dose of 1.0 mg/m(2) in patients previously treated for HNC and 1.3 mg/m(2) in radiation-naive patients.

Safety and efficacy of autologous bone marrow stem cell transplantation through hepatic artery for the treatment of chronic liver failure: a preliminary study.

This study was performed to determine the safety and tolerability of injecting autologous bone marrow stem cells (BMC) (CD34+) into four patients with liver insufficiency. The study was based on the hypothesis that the CD34+ cell population in granulocyte colony stimulating factor (G-CSF) mobilized blood and autologous bone marrow contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated the CD34+ stem cell population from the bone marrow. The potential of the BMC to differentiate into hepatocytes and other cell lineages has already been reported. Several reports have also demonstrated the plasticity of hematopoietic stem cells to differentiate into hepatocytes. Recently Sakaida demonstrated reduction in fibrosis in chemically induced liver cirrhosis following BMC transplantation. From a therapeutic point of view, chronic liver cirrhosis is one of the targets for BMC transplantation. In this condition, there is excessive deposition of extracellular matrix and hepatocyte necrosis. Encouraged by this evidence that the CD34+ cell population contains cells with the potential to form hepatocyte-like elements, four patients with liver insufficiency were given G-CSF to mobilize stem cells. CD34+ cells (0.1 x 10(8)) were injected into the hepatic artery. No complications or specific side effects related to the procedure were observed; four patients showed improvements in serum albumin, bilirubin and ALT after one month from the cell infusion.