Oxaliplatin-related dysphagia: Mixed-methods study.

OBJECTIVES: To evaluate participant-reported atypical dysphagia symptoms and their association with oxaliplatin treatment. METHODS: This observational study recruited 73 adults with solid tumours outside the head, neck or upper gastrointestinal tract. All had dysphagia, were in hospital or hospice and were treated by Medical Oncology, Radiation Oncology or Palliative Care. Participants reported their experiences of swallowing difficulties by semistructured interview. Oral Health Assessment Tool was used to ensure swallow difficulties were not due to mucositis. Responses were transcribed and analysed by content analysis. Atypical difficulties were examined for association with oxaliplatin treatment by Fischer's Exact. RESULTS: Oxaliplatin treatment was associated with three unusual dysphagia symptoms: problems with cold or hot bolus (p=0.01), pins and needles (p=0.001) and throat spasm (p=0.035). Carbonation was problematic for one participant. Chemotherapy commencement coincided with swallow problem onset for 67%. Dysphagia symptoms were unrelated to mucositis (p=0.165). CONCLUSIONS: Swallowing difficulties in oxaliplatin-treated patients are atypical and attributable to chemotherapy commencement. Previous research suggests that dysphagia is triggered by cold exposure, but hot and carbonated boluses also caused problems here. Dysphagia symptoms and triggers should be studied more fully to help patients safely enjoy their meals and prevent food avoidance, which could exacerbate malnutrition.

Interobserver Variability of Gross Tumor Volume Delineation for Colorectal Liver Metastases Using Computed Tomography and Magnetic Resonance Imaging.

Purpose: The purpose of this study was to evaluate the interobserver variability in the contouring of the gross tumor volume (GTV) on magnetic resonance (MR) imaging and computed tomography (CT) for colorectal liver metastases in the setting of SABR. Methods and Materials: Three expert radiation oncologists contoured 10 GTV volumes on 3 MR imaging sequences and on the CT image data set. Three metrics were chosen to evaluate the interobserver variability: the conformity index, the DICE coefficient, and the maximum Hausdorff distance (HDmax). Statistical analysis of the results was performed using a 1-sided permutation test. Results: For all 3 metrics, the MR liver acquisition volume acquisition (MR LAVA) showed the lowest interobserver variability. Analysis showed a significant difference (P < .01) in the mean DICE, an overlap metric, for MR LAVA (0.82) and CT (0.74). The HDmax that highlights boundary errors also showed a significant difference (P = .04) with MR LAVA having a lower mean HDmax (7.2 mm) compared with CT (5.7 mm). The mean HDmax for both MR single shot fast spin echo (SSFSE) (19.3 mm) and diffusion weighted image (9.5 mm) showed large interobserver variability with MR SSFSE having a mean HDmax of 19.3 mm. A volume comparison between MR LAVA and CT showed a significantly higher volume for small GTVs (<5 cm3) when using MR LAVA for contouring in comparison to CT. Conclusions: This study reported the lowest interobserver variability for the MR LAVA, thus indicating the benefit of using MR to complement CT when contouring GTV for colorectal liver metastases.

Implementation of advanced radiotherapy techniques: stereotactic body radiotherapy (SBRT) for oligometastatic patients with lung metastasis - a single institution experience.

Background and aims: The treatment of oligometastatic disease has become common practice as advanced radiotherapy techniques became more available. Lung is one of the main metastatic sites for a majority of cancers and many of these patients present with a limited metastatic disease burden. For these patients, SBRT (Stereotactic Body Radiation Therapy) represents a non-invasive treatment alternative. In this report we present our experience with our first series of patients with limited metastatic disease treated with lung SBRT. The purpose of this paper is to provide a qualitative and quantitative assessment of the lung SBRT treatment process and algorithm leading up to treatment delivery in a community-based radiotherapy department. Methods: We have retrospectively reviewed our first series of 41 patients with lung oligometastases from various malignancies, treated using SBRT between March 2019 and December 2020. Demographic, technical and outcome data were analyzed. Results: A number of 45 lung metastases (in 41 patients) were treated with SBRT during the specified time period. The median age was 65.7 years old (range 33-83). 16 patients (39%) were treated for multiple lesions and the mean number of treated lesions was 1 (range1-3). Median dose prescribed was 50 Gy /5 fractions (median BED10 =77 Gy). The median intra-fraction displacements were: Vertical (0.23cm), Longitudinal (-0.27 cm), Lateral (-0.1 cm), Pitch [0.22°], Roll [0.15°], Rotation [0.32°]. The median session time was 40 minutes. All patients completed the prescribed course of treatment.Preliminary clinical data were recorded. With a median follow-up of 9 months, local control was recorded in all but one patient. At the last known follow-up, local control was recorded for 39 (85%) out of 45 treated lesions. Conclusion: For lung SBRT, the required corrections at the time of treatment delivery are small, as long as strict protocols are implemented. Preliminary data for lung metastasis in oligometastatic patients support SBRT as a viable method of achieving high rates of early local control. These results need to be further confirmed in a larger cohort of patients with longer follow-up.

Dysphagia in Solid Tumors Outside the Head, Neck or Upper GI Tract: Clinical Characteristics.

CONTEXT: Dysphagia is common in cancer, but underlying pathophysiology and manifestations within patients are unknown. OBJECTIVES: To examine dysphagia characteristics in those with solid malignancies outside the head, neck and upper gastrointestinal tract. METHODS: Seventy-three individuals with dysphagia (46 male, 27 female, aged 37-91) were recruited from a parent trial conducted in two acute hospitals and one hospice. Cranial nerve function, Oral Health Assessment Tool (OHAT), Mann Assessment of Swallowing Ability (MASA) and Functional Oral Intake Scale (FOIS) evaluated swallow profile. RESULTS: Only 9/73 (12%) had documented dysphagia prior to study enrollment. MASA risk ratings found n=61/73 (84%) with dysphagia risk and n=22/73 (30%) with aspiration risk. Food texture modification was required for n=34/73 (47%), fluid texture modification for n=1/73 (1%). Compensatory strategies for food were needed by n=13/73 (18%) and for fluids by n=24/73 (33%). Cranial nerve deficits were present in n=43/73 (59%). Oral health problems were common, with xerostomia in two-thirds. Worse dysphagia on MASA was associated with disease progression, affecting hospice, and palliative care the most. Worse performance status was indicative of poorer MASA raw score (P<0.001, OR 2.2, 95% CI 1.5-3.4), greater risk of aspiration (P=0.005, OR 2.1, 95% CI 1.3-3.6) and lower FOIS (P=0.004, OR 2.0, 95% CI 1.2-3.2). CONCLUSION: Dysphagia management in those with cancer requires robust assessment to uncover clinically important needs like food texture modification and safe swallowing advice. Better assessment tools should be developed for this purpose. Oral health problems should be routinely screened in this population since they exacerbate dysphagia.

Technical challenges of linac-based stereotactic ablative body radiotherapy: short review for non-radiation oncologists.

Stereotactic ablative radiotherapy (SABR) is a radiation technique delivering high doses of radiation in a small number of treatments, to extracranial targets. It is standard of care in patients with inoperable early stage non-small cell lung cancer, and it is increasingly used in patients with oligometastatic disease. The main advantage of SABR is a steep dose gradient, allowing delivery of high biologically effective doses to the target, while minimizing irradiation exposure of the neighboring normal tissues. This results in high rates of local control of the treated target and minimal toxicity risks, and minimal impact on the quality of life of the patients. However, it requires high precision, accuracy and reproducibility during the entire process, from simulation to treatment planning and treatment delivery. This article will focus on general principles of SABR treatment planning and delivery, with emphasis on the strategies to reduce errors related to immobilization, respiratory management and treatment verification.

Understanding and Attitudes toward Cancer Clinical Trials among Patients with a Cancer Diagnosis: National Study through Cancer Trials Ireland.

Cancer clinical trials (CCTs) are critical to translation and development of better therapies to improve outcomes. CCTs require adequate patient involvement but accrual rates are low globally. Several known barriers impede participation and knowing how subpopulations differ in understanding of CCTs can foster targeted approaches to aid accrual and advance cancer treatments. We conducted the first nationwide survey of 1089 patients attending 14 Irish cancer centres, assessing understanding of fundamental concepts in CCT methodology and factors that influence participation, to help tailor patient support for accrual to CCTs. Two-thirds (66%) of patients reported never having been offered a CCT and only 5% of those not offered asked to participate. Misunderstanding of clinical equipoise was prevalent. There were differences in understanding of randomisation of treatment by age (p < 0.0001), ethnicity (p = 0.035) and marital status (p = 0.013), and 58% of patients and 61% previous CCT participants thought that their doctor would ensure better treatment in CCTs. Females were slightly more risk averse. Males indicated a greater willingness to participate in novel drug trials (p = 0.001, p = 0.003). The study identified disparities in several demographics; older, widowed, living in provincial small towns and fewer years-educated patients had generally poorer understanding of CCTs, highlighting requirements for targeted support in these groups.

Stereotactic body radiotherapy in patients with multiple lung tumors: a focus on lung dosimetric constraints.

Introduction: Lung dosimetric constraints with stereotactic body/ablative radiotherapy (SBRT/SABR) for multiple lung lesions are not well-characterized in published literature. Classically, the lung is considered a 'parallel' organ, for which injury to functional subunits could result in partially compromised function of that organ/tissue. Therefore, with SBRT/SABR for >1 thoracic target (especially involving both lungs), lung dosimetry requires special consideration.Areas covered: Current cooperative group and multi-institutional studies of SBRT/SABR for oligometastases rely on lung constraints from expert opinion, including constraints of exposure (i.e., volume of lung receiving more than a threshold dose or mean lung dose) and/or critical volume (i.e. volume of lung receiving less than a threshold dose; also termed complementary volume). For radiation pneumonitis, which reflects inflammatory lung injury, it remains unclear which type of constraint is more predictive of toxicity risks.Expert opinion: With SBRT/SABR for multiple lung lesions, it is prudent to use both exposure and critical volume constraints. Treatment on alternate days (for radiation plans with separate treatment fields) or staging treatment may also lower lung toxicity risks. Further study on lung normal tissue complication probability in the setting of multiple lung targets is urgently needed, particularly analyses of critical volume metrics, which are relatively poorly studied.

Dysphagia Prevalence and Predictors in Cancers Outside the Head, Neck, and Upper Gastrointestinal Tract.

CONTEXT: Dysphagia is usually associated with malignancies of the head, neck, and upper gastrointestinal tract but also occurs in those with tumors outside anatomic swallow regions. It can lead to aspiration pneumonia, malnutrition, reduced quality of life, and psychosocial distress. No studies have yet reliably described dysphagia prevalence in those with malignancies outside anatomic swallow regions. OBJECTIVE: The objective of this study was to establish the prevalence and predictors of dysphagia in adults with solid malignancies outside the head, neck, and upper gastrointestinal tract. METHODS: A cross-sectional, observational study using consecutive sampling was conducted. There were 385 participants (mean age 66 ± 12 years) with 21 different primary cancer sites from two acute hospitals and one hospice. Locoregional disease was present in 33%, metastatic in 67%. Dysphagia was screened by empirical questionnaire and confirmed through swallow evaluation. Demographic and clinical predictors were determined by univariate and multivariate binary regression. RESULTS: Dysphagia occurred in 19% of those with malignancies outside anatomic swallow regions. Prevalence was 30% in palliative care and 32% in hospice care. Dysphagia was most strongly associated with cough, nausea, and worse performance status. It was also associated with lower quality of life and nutritional difficulties. CONCLUSION: Dysphagia was common and usually undiagnosed before study participation. It occurred at all disease stages but coincided with functional decline. It may therefore represent a cancer frailty marker. Oncology and palliative care services should routinely screen for this symptom. Timely dysphagia identification and management may improve patient well-being and prevent adverse effects like aspiration pneumonia and weight loss.

Linac-Based Radiosurgery for Patients With Brain Oligometastases From a Breast Primary, in the Trastuzumab Era-Impact of Tumor Phenotype and Prescribed SRS Dose.

Background: The role of stereotactic radiosurgery (SRS) in the treatment of limited numbers of brain metastases in selected breast cancer patients is well-established. Aims: To analyse outcome from a single institutional experience with SRS, to identify any significant prognostic factors and to assess the influence of Her-2, estrogen receptor status, and prescribed dose on outcome. Methods: The medical records of 56 patients treated at in a single institution between 2009 and 2014 were reviewed. Demographic, treatment related and outcome data were analyzed to identify prognostic factors in this patient population. The primary endpoints were overall survival and local control. Secondary endpoint was distant intra-cranial progression-free survival. Results: The median follow- up time for the entire cohort was 10.33 months (1.25-97.28). The overall median survival was 12.5months (95%CI = 5.8-19.2), with 53.3%, and 35.8% surviving at 1- and 2- years post-SRS. After adjustment for the effect of Her 2 status, uncontrolled extra-cranial disease at the time of SRS predicted for shorter survival (HR for death = 3.1, 95% CI = 1.4-6.9, p = 0.006). At the time of death, 75% of the patients had active, uncontrolled intra-cranial disease, with 56% these patients presenting intra-cranial disease only. Sustained local control was observed in 56 (59.6%) of 94 treated metastases. In univariate analysis, Her2 status, ERHer2 group status?, and prescribed SRS dose were highly significant for local progression free-survival (LPFS). After adjustment for the effect of Her 2 status, patients receiving 12-16 Gy can expect shorter LPFS than those receiving 18-20 Gy (HR = 1.7, 95% CI = 1.0-2.8, p = 0.043). After adjustment for the effect of dose group, patients with Her 2 negative cancer can expect shorter LPFS than those with Her 2 positive cancer (HR = 2.6, 95% CI = 1.5-4.4, p < 0.0005). Use of prior WBRT did not impact survival, local or distant intra-cranial progression-free survival. Conclusions: Survival outcome is similar to the published literature. Improved outcomes are observed in patients with Her 2-positive, controlled extracranial disease at the time of SRS and higher SRS dose delivered. Achieving intra-cranial control appears to be an important factor for the survival of the breast cancer patients in the era of targeted therapies.

Stereotactic Ablative Radiation Therapy for Unresectable Colorectal Oligometastases.

PURPOSE: Patients with oligometastatic colorectal cancer have demonstrated excellent clinical outcomes with surgical resection of hepatic and pulmonary metastases. Stereotactic ablative radiation therapy (SABR) has emerged as an alternative local therapy for nonsurgical candidates. Herein, we report the oncologic and patient-reported quality-of-life (PR-QoL) outcomes for a subset of patients with oligometastatic colorectal cancer who were treated in a prospective phase 2 multicenter clinical trial. METHODS AND MATERIALS: Patients with a pathologically proven diagnosis of oligometastatic colorectal cancer were enrolled as part of a prospective study. SABR dose and fractionation schedules were dependent on the lesion location and size. Patient follow-up occurred 6 weeks after completion of SABR and at 3-month intervals for the following 3 years. Patients received the Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up visit to assess PR-QoL. The total Functional Assessment of Cancer Therapy-General questionnaire scores were compared with those from baseline using the Wilcoxon signed rank test. Overall survival, local progression-free survival (PFS), and distant PFS were calculated using the Kaplan-Meier estimation to the date of the last follow-up visit/death or local/distant failure. RESULTS: A total of 31 patients with oligometastatic colorectal cancer with 1 (71.0%), 2 (16.1%), 3 (3.2%), 4 (3.2%), or 5 (6.5%) metastatic lesions were identified. After a median follow-up time of 50.1 months, the median OS from the time of completion of the SABR was 53.9 months (95% confidence interval, 23.2-84.6), and the 5-year OS, local PFS, and distant PFS were 45%, 83%, and 27%, respectively. Acute grade 2+ toxicity was 9.7% (pain, nausea, fatigue) and late grade 3+ toxicity (small bowel obstruction) was 3.2% with no significant change in PR-QoL in the year after SABR. CONCLUSIONS: This subset analysis of a prospective phase 2 study demonstrates that SABR is a safe and effective treatment option for patients with unresectable oligometastic colorectal cancer. In addition, SABR of oligometastatic disease preserves PR-QoL.

Initial Results of a Multicenter Phase 2 Trial of Stereotactic Ablative Radiation Therapy for Oligometastatic Cancer.

PURPOSE: Oligometastatic disease has emerged as a potentially curable state in the spectrum of cancer progression. Aggressive local therapy such as stereotactic ablative radiation therapy (SABR) may improve oncologic outcomes. Herein, we report the initial oncologic outcomes and patient-reported quality of life (PR-QoL) from a phase 2 multicenter trial for patients with oliogmetastatic disease. METHODS AND MATERIALS: Patients with oligometastatic disease (1-5 metastases) were prospectively recruited between 2011 and 2017. SABR dose and fractionation was dependent on the lesion size and location. Patient follow-up occurred within 6 weeks of completion of SABR and at 3-month intervals. Patients received a Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up to assess for PR-QoL. Median follow-up was calculated by reverse Kaplan-Meier method. Overall survival (OS), local progression-free survival, and distant progression-free survival were calculated using the Kaplan-Meier method. RESULTS: We enrolled 147 patients with oligometastatic cancer with a median age of 66.4 years (interquartile range, 59.9-74.6). The most common primary tumors included lung (21.8%, non-small cell: n = 29, small cell: n = 3), colorectal adenocarcinoma (21.1%), and head and neck (10.9%, squamous cell carcinoma: n = 11). In a median follow-up of 41.3 months (interquartile range: 14.6-59.0), the median OS was 42.3 months (95% confidence interval: 27.4-∞) with 5-year OS of 43%. Five-year local progression-free survival and distant progression-free survival were 74% and 17%, respectively. Acute grade 2+ and 3+ toxicity were 7.5% and 2.0%, respectively, and late grade 2+ and 3+ toxicity were both 1.4%. There was no significant change in quality of life at completion and 6 weeks, 3 months, and 9 months after treatment. At 6 and 12 months, patients were found to have statistically significant improvement in PR-QoL. CONCLUSIONS: This multicenter prospective phase 2 study demonstrates that SABR for recurrent oligometastatic cancer is a feasible and tolerable treatment option with minimal acute and late grade 3 toxicity. Additionally, PR-QoL was not adversely affected.

Treatment completion, treatment compliance and outcomes of old and very old patients treated by dose adapted stereotactic ablative radiotherapy (SABR) for T1-T3N0M0 non-small cell lung cancer.

AIM: This is a retrospective single-institution review of the treatment completion and clinical outcomes of patients aged 75 and older, treated with stereotactic ablative body radiotherapy (SABR) for T1-T3 N0 M0 non-small cell lung cancer (NSCLC). METHODS: From April 2008 to September 2015, 200 patients, aged 75-93, received respiratory-managed, intensity-modulated-based SABR. Dose fractionation was risk-adapted and delivered in 2-3 weekly treatments. Treatment completion, local control, overall survival and treatment-related toxicities were evaluated. RESULTS: All patients completed the prescribed SABR course. However, 29 patients required interruption of at least one fraction of SABR and optimization of pain control before continuation of the fraction. Median follow-up was 20.9 months. The median OS was 31.6 months with 1-,3-year survival rates of 80.7%, and 44.4% respectively. Local control at 1- and 3- years were 97.6%, 83.5% respectively. Treatment was well-tolerated. However, there were two (1%) G5 (fatal) toxicities: one acute sudden dyspnoea of unknown cause and one late SABR-related haemoptysis. No statistically significant differences in outcomes/toxicities were observed between old (75-84 years old) and very old patients (>85 years old). CONCLUSIONS: Old and very old patients can successfully complete SABR for NSCLC, with good local control, survival and acceptable toxicity. Old patients might require increased supportive care for successful treatment delivery.

Review of thoracic reirradiation with stereotactic body radiation therapy: A focus on toxicity risks.

Reirradiation of thoracic malignancies is clinically challenging in balancing the risks and efficacy. Stereotactic body radiation therapy (SBRT) can facilitate ablative dosing of discrete targets while minimizing normal tissue exposure; thus, SBRT is an attractive, minimally invasive option to consider for patients with recurrent or new malignancies within a previously irradiated field. Published data are summarized from 28 studies on the use of SBRT for thoracic reirradiation. We review clinical outcomes with a primary focus on toxicity risks, dosimetric correlates of normal tissue complication probability (NTCP), and other factors that correlate with NTCP. Meaningful compilation of published data on reirradiation with SBRT is limited because of the retrospective nature of published studies, which include mostly small numbers of patients, with various clinical scenarios and SBRT dosing and techniques. Nevertheless, these studies show that thoracic reirradiation with SBRT is feasible, with relatively favorable outcomes. Yet, severe to fatal toxicities do occur, and dosimetric measures to predict severe toxicity are poorly characterized, necessitating further study to better characterize predictive factors for NTCP.

Late Toxicity and Outcomes in High-risk Prostate Cancer Patients Treated With Hypofractionated IMRT and Long-term Androgen Suppression Treatment.

OBJECTIVE: To assess late toxicity and outcomes in high-risk prostate cancer patients treated with hypofractionated radiation treatment with androgen suppression therapy. METHODS: Sixty high-risk prostate cancer patients were enrolled. IMRT prescription was 68 Gy/25 fractions (2.7 Gy/fraction) to the prostate and proximal seminal vesicles (SV). The pelvic lymph nodes (PLN) and distal SV concurrently received 45 Gy/25 fractions (1.8 Gy/fraction). The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification before each treatment. RTOG Toxicity scores were recorded for a 5-year period. RESULTS: Sixty patients completed RT with median follow-up of 63 months (range, 7 to 80 mo).At 5 years follow-up timepoint: Grade (G)2 and G3 late genitourinary toxicity was experienced in 7 (17.0%) and 1 (2.44%), respectively; gastrointestinal G2 as highest toxicity recorded in only 1 (2.44%) patient. There was no G3 gastrointestinal toxicity recorded at this timepoint.With 63-month median follow-up (mean of 65.41±1.72 mo), the 5-year overall survival was 86.67%; 5 years freedom from biochemical failure was 91.67% and freedom from clinical failure was 96.67%. CONCLUSIONS: Dose escalation and hypofractionated radiation treatment with IMRT treating the prostate and proximal SV concurrently with the pelvic lymph nodes and distal SV and long-term androgen suppression therapy is well tolerated with respect to acute and late toxicity with 5-year actuarial overall survival 86.67%, freedom from biochemical failure 91.38%, and freedom from clinical failure 96.67%. Longer follow-up will provide more information on 10-year survival outcomes.

Patients with colorectal lung oligometastases (L-OMD) treated by dose adapted SABR at diagnosis of oligometastatic disease have better outcomes than patients previously treated for their metastatic disease.

AIM: To evaluate the clinical outcomes of patients with OMD from a CRC primary, who underwent SABR either as first treatment at diagnosis of metachronous oligometastatic disease to lung or at progression in lung after prior treatments for metastatic disease. METHODS: This is a retrospective review of 60 patients with 85 lung oligometastases treated by SABR at two institutions, between May 2009 and September 2014. Local control (LC), overall survival (OS), progression - free survival (PFS), and toxicity were evaluated. RESULTS: Median follow-up was 22.9±15.5 months (range: 2.6-68.6). For the entire cohort, LC was observed for 76.6% of the target lesions; the 2- year OS and PFS were 77% and 28 % respectively. After a median of 7.9 months from SABR, 39 patients presented a first progression. In univariate analysis, patients with multiple recurrences prior to SABR (p=0.001) and those who received chemotherapy for metastatic progression (p=0.014) had poorer PFS from time of SABR. Median PFS for patients with no prior treatment for L-OMD vs. prior chemotherapy +/- local treatment vs. local treatment only was: not reached vs. 8.83 (± 2) vs. 32.5 (±2.75) months. The main pattern of first progression was out of field progression: in-field progression alone occurred in 7 patients (12%) and with synchronous regional/distant progression in 10 patients (17%. In all patients, chemotherapy was withheld until progression post-SABR. Treatment was well tolerated; only one patient experienced grade 3 bronchial toxicity, three months after completion of SABR. CONCLUSIONS: SABR achieves high rates of local control with limited toxicities in patients with lung oligometastatic disease from a colorectal primary. This retrospective data indicates that patients with newly diagnosed lung oligometastatic disease may be safely treated with SABR as first treatment, with chemotherapy held in reserve. In heavily pretreated patients, SABR may allow patients a treatment break from systemic therapy, which may be beneficial both psychologically and physically. Future randomized SABR studies should evaluate sequencing of chemotherapy, the role of immunotherapies, and the quality of life of patients undergoing SABR.

Antibacterial structure-activity relationship studies of several tricyclic sulfur-containing flavonoids.

A structure-activity relationship study concerning the antibacterial properties of several halogen-substituted tricyclic sulfur-containing flavonoids has been performed. The compounds have been synthesized by cyclocondensation of the corresponding 3-dithiocarbamic flavanones under acidic conditions. The influence of different halogen substituents on the antibacterial properties has been tested against Staphylococcus aureus and Escherichia coli. Amongst the N,N-dialkylamino-substituted flavonoids, those having an N,N-diethylamino moiety exhibited good to excellent antimicrobial properties against both pathogens. Fluorine-substituted flavonoids were found to be less active than those bearing other halogen atoms.

Dosimetric effect of small bowel oral contrast on conventional radiation therapy, linear accelerator-based intensity modulated radiation therapy, and helical tomotherapy plans for rectal cancer.

PURPOSE: This study evaluated the dosimetric effect of small bowel oral contrast on conventional radiation therapy, linear accelerator-based intensity modulated radiation therapy (IMRT), and helical tomotherapy (HT) treatment plans. METHODS AND MATERIALS: Thirteen patients with rectal cancer underwent computed tomography (CT) simulation with oral contrast (CCT) in preparation for chemoradiation therapy. The contrast in the small bowel was contoured, and a noncontrast CT scan (NCCT) was simulated by reassigning a CT number of 0 Hounsfield units to the contrast volume. Conventional, IMRT, and HT plans were generated with the CCT. The plan generated on the CCT was then recalculated on the NCCT, maintaining the same number of monitor units for each field, and the plans were not renormalized. Dosimetric parameters representing coverage of the planning target volume with 45 Gy (D98%, D95%, D50%, and D2%) and sparing of the bladder and peritoneal cavity (D50%, D30%, and D10%) were recorded. The ratio of dose calculated in the presence of contrast to dose with contrast edited out was recorded for each parameter. A paired Student t test was used for comparison of plans. RESULTS: For conventional plans, there was <0.1% variance in the dose ratio for all volumes of interest. For IMRT plans, there was a 1% decrease in the mean dose ratio, and the range of dose ratios for all volumes was greater than that for HT or conventional plans. For HT plans, for all volumes of interest, the mean dose ratio was <0.2%, and the range for all patients was <1%. For all IMRT dosimetric parameters, the difference was in the order of 1% of the mean dose (P < .05). The dose difference was not statistically significant for the conventional or HT plans. CONCLUSIONS: The use of CCT during CT simulation has no clinically significant effect on dose calculations for conventional, IMRT, and HT treatment plans and may not require replacement of the contrast with a CT number of 0 Hounsfield units.

Acute toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated intensity-modulated radiotherapy.

PURPOSE: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. METHODS AND MATERIALS: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of > or =T3a or an initial prostate-specific antigen [PSA] level of > or =20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. RESULTS: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. CONCLUSION: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

Skin-sparing radiation using intensity-modulated radiotherapy after conservative surgery in early-stage breast cancer: a planning study.

PURPOSE: To evaluate the feasibility of skin-sparing by configuring it as an organ-at-risk (OAR) while delivering whole-breast intensity-modulated radiotherapy (IMRT) in early breast cancer. METHODS AND MATERIALS: Archival computed tomography scan images of 14 left-sided early-breast tumor patients who had undergone lumpectomy were selected for this study. Skin was contoured as a 4- to 5-mm strip extending from the patient outline to anterior margin of the breast planning target volume (PTV). Two IMRT plans were generated by the helical tomotherapy approach to deliver 50 Gy in 25 fractions to the breast alone: one with skin dose constraints (skin-sparing plan) and the other without (non-skin-sparing plan). Comparison of the plans was done using a two-sided paired Student t test. RESULTS: The mean skin dose and volume of skin receiving 50 Gy were significantly less with the skin-sparing plan compared with non-skin-sparing plan (42.3 Gy vs. 47.7 Gy and 12.2% vs. 57.8% respectively; p < 0.001). The reduction in skin dose was confirmed by TLD measurements in anthropomorphic phantom using the same plans. Dose-volume analyses for other OARs were similar in both plans. CONCLUSIONS: By configuring the skin as an OAR, it is possible to achieve skin dose reduction while delivering whole-breast IMRT without compromising dose profiles to PTV and OARs.