Exploring gender differences in the relationship between gut microbiome and depression - a scoping review.

Background: Major depressive disorder (MDD) exhibits gender disparities, and emerging evidence suggests the involvement of the gut microbiome, necessitating exploration of sex-specific differences. Methods: A review was conducted, encompassing a thorough examination of relevant studies available in Medline via Ovid, Embase via OvidSP, CINAHL, and PsycINFO databases from their inception to June 2023. The search strategy employed specific keywords and Medical Subject Headings (MeSH) terms tailored to major depressive disorder in women, encompassing unipolar depression, depressive symptoms, and dysbiosis. Results: Five studies were included. Among the four studies, alterations in alpha (n=1) and beta diversity (n=3) in the gut microbiome of individuals with MDD were revealed compared to controls. Gender-specific differences were observed in four studies, demonstrating the abundance of specific bacterial taxa and highlighting potential sex-specific implications in MDD pathophysiology. Correlation analyses (n=4) indicated associations between certain bacterial taxa and the severity of depressive symptoms, with varying patterns between males and females. Studies (n=3) also highlighted promising findings regarding the potential utility of microbial markers in diagnosing MDD, emphasizing the crucial role of sex stratification in understanding the disease pathophysiology. Conclusions: The findings underscore the importance of recognizing gender-specific differences in the composition of the gut microbiome and its relationship with MDD. Further comprehensive robust studies are required to unravel the intricate mechanisms underlying these disparities.

BRAVEHeart: a randomised trial comparing the accuracy of Breathe Well and RPM for deep inspiration breath hold breast cancer radiotherapy.

BACKGROUND: Deep inspiration breath hold (DIBH) reduces radiotherapy cardiac dose for left-sided breast cancer patients. The primary aim of the BRAVEHeart (Breast Radiotherapy Audio Visual Enhancement for sparing the Heart) trial is to assess the accuracy and usability of a novel device, Breathe Well, for DIBH guidance for left-sided breast cancer patients. Breathe Well will be compared to an adapted widely available monitoring system, the Real-time Position Management system (RPM). METHODS: BRAVEHeart is a single institution prospective randomised trial of two DIBH devices. BRAVEHeart will assess the DIBH accuracy for Breathe Well and RPM during left-sided breast cancer radiotherapy. After informed consent has been obtained, 40 patients will be randomised into two equal groups, the experimental arm (Breathe Well) and the control arm (RPM with in-house modification of an added patient screen). The primary hypothesis of BRAVEHeart is that the accuracy of Breathe Well in maintaining the position of the chest during DIBH is superior to the RPM system. Accuracy will be measured by comparing chest wall motion extracted from images acquired of the treatment field during breast radiotherapy for patients treated using the Breathe Well system and those using the RPM system. DISCUSSION: The Breathe Well device uses a depth camera to monitor the chest surface while the RPM system monitors a block on the patient's abdomen. The hypothesis of this trial is that the chest surface is a better surrogate for the internal chest wall motion used as a measure of treatment accuracy. The Breathe Well device aims to deliver an easy-to-use implementation of surface monitoring. The findings from the study will help inform the technology choice for other centres performing DIBH. TRIAL REGISTRATION: ClinicalTrials.gov NCT02881203 . Registered on 26 August 2016.

Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: A systematic review with network meta-analysis.

Aromatase inhibitor-induced arthralgia (AIA) contributes to poor adherence of aromatase inhibitor therapies in patients with breast cancer. A systematic review using network meta-analysis (NMA) was conducted to examine the clinical effectiveness of multiple therapies and rank probabilities for the management of AIA. Randomized controlled trials (RCTs) assessing treatments for AIA in postmenopausal women with stage 0-III hormone receptor-positive breast cancer were searched from inception to October 2021. The main NMA involved 1516 participants from 17 RCTs. Acupuncture was the highest ranked intervention to improve pain intensity followed by sham acupuncture, multicomponent herbal medicine, exercise, duloxetine, vitamin D, omega-3 fatty acids, physical therapy, testosterone, and inactive controls. Single natural products were inferior to controls. The current review provides new insights into the management of AIA in breast cancer survivors for increased survival and can be utilized to make evidence-based decisions regarding treatment.

Potential gains: Comparison of a mono-isocentric three-dimensional conformal radiotherapy (3D-CRT) planning technique to hybrid intensity-modulated radiotherapy (hIMRT) to the whole breast and supraclavicular fossa (SCF) region.

INTRODUCTION: Until late 2018, standard of practice at the Northern Sydney Cancer Centre (NSCC) for breast and nodal treatment was a conformal mono-isocentric technique. A planning study comparing an existing mono-isocentric three-dimensional conformal radiotherapy (3D-CRT) planning technique to a hybrid intensity-modulated radiotherapy (hIMRT) approach for the whole breast and supraclavicular fossa (SCF) region was undertaken with the aim to improve plan quality by improving dose conformity/homogeneity across target volumes and reducing hotspots outside the target. METHODS: A cohort of 17 patients was retrospectively planned using the proposed hIMRT technique, keeping the same planning constraints as the original treated breast and SCF 3D-CRT plan and normalising the 3D-CRT plans to achieve minimum breast/SCF target coverage to compare organs at risk (OARs). Normal tissue index (NTI) and homogeneity index (HI) were compared for plan quality as well as for evaluating OARs. RESULTS: The hIMRT technique showed statistically significant improvements in NTI and HI, as well as improvement in maximum brachial plexus and thyroid doses. There was a negligible increase in maximum oesophagus dose which could be improved if used in optimisation. Other OAR doses in the irradiated region were comparable to the 3D-CRT plans, however maximum doses were reduced overall. CONCLUSION: The hIMRT planning technique maintained clinically acceptable doses to OARs and reduced normal tissue dose while maintaining equivalent dose coverage to breast and SCF planning target volumes with improved conformity and homogeneity. The reduction in maximum doses promotes a favourable toxicity profile, with potential benefit of improved long-term cosmesis.

Comprehensive nodal breast VMAT: solving the low-dose wash dilemma using an iterative knowledge-based radiotherapy planning solution.

INTRODUCTION: Aimed to develop a simple and robust volumetric modulated arc radiotherapy (VMAT) solution for comprehensive lymph node (CLN) breast cancer without increase in low-dose wash. METHODS: Forty CLN-breast patient data sets were utilised to develop a knowledge-based planning (KBP) VMAT model, which limits low-dose wash using iterative learning and base-tangential methods as benchmark. Another twenty data sets were employed to validate the model comparing KBP-generated ipsilateral VMAT (ipsi-VMAT) plans against the benchmarked hybrid (h)-VMAT (departmental standard) and bowtie-VMAT (published best practice) methods. Planning target volume (PTV), conformity/homogeneity index (CI/HI), organ-at-risk (OAR), remaining-volume-at-risk (RVR) and blinded radiation oncologist (RO) plan preference were evaluated. RESULTS: Ipsi- and bowtie-VMAT plans were dosimetrically equivalent, achieving greater nodal target coverage (P < 0.05) compared to h-VMAT with minor reduction in breast coverage. CI was enhanced for a small reduction in breast HI with improved dose sparing to ipsilateral-lung and humeral head (P < 0.05) at immaterial expense to spinal cord. Significantly, low-dose wash to OARs and RVR were comparable between all plan types demonstrating a simple VMAT class solution robust to patient-specific anatomic variation can be applied to CLN breast without need for complex beam modification (hybrid plans, avoidance sectors or other). This result was supported by blinded RO review. CONCLUSIONS: A simple and robust ipsilateral VMAT class solution for CLN breast generated using iterative KBP modelling can achieve clinically acceptable target coverage and OAR sparing without unwanted increase in low-dose wash associated with increased second malignancy risk.

Cardiovascular Manifestations From Therapeutic Radiation: A Multidisciplinary Expert Consensus Statement From the International Cardio-Oncology Society.

Radiation therapy is a cornerstone of cancer therapy, with >50% of patients undergoing therapeutic radiation. As a result of widespread use and improved survival, there is increasing focus on the potential long-term effects of ionizing radiation, especially cardiovascular toxicity. Radiation therapy can lead to atherosclerosis of the vasculature as well as valvular, myocardial, and pericardial dysfunction. We present a consensus statement from the International Cardio-Oncology Society based on general principles of radiotherapy delivery and cardiovascular risk assessment and risk mitigation in this population. Anatomical-based recommendations for cardiovascular management and follow-up are provided, and a priority is given to the early detection of atherosclerotic vascular disease on imaging to help guide preventive therapy. Unique management considerations in radiation-induced cardiovascular disease are also discussed. Recommendations are based on the most current literature and represent a unanimous consensus by the multidisciplinary expert panel.

The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?

Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for "cancer" and "immunotherapy/immune checkpoint inhibitor" and "microbiome/microbiota" and/or "fecal microbiome transplant FMT". The relevant literature was selected for this article. Results: Ten studies examined patients diagnosed with advanced metastatic melanoma (n = 6), hepatocellular carcinoma (HCC) (n = 2), non-small cell lung carcinoma (NSCLC) (n = 1) and one study examined combination both NSCLC and renal cell carcinoma (RCC) (n = 1). These studies consistently reported that the gut microbiome profile prior to administering immune checkpoint inhibitors (ICIs) was related to clinical response as measured by progression-free survival (PFS) and overall survival (OS). Two studies reported that a low abundance of Bacteroidetes was associated with colitis. Two studies showed that patients with anti-PD-1 refractory metastatic melanoma experienced improved response rates and no added toxicity when receiving fecal microbiota transplant (FMT) from patients with anti-PD-1 responsive disease. Conclusions: Overall, significant differences in the diversity and composition of the gut microbiome were identified in ICIs responders and non-responders. Our findings provide new insights into the value of assessing the gut microbiome in immunotherapy. Further robust randomized controlled trials (RCTs) examining the modulatory effects of the gut microbiome and FMT on ICIs in patients not responding to immunotherapy are warranted.

Emerging Evidence of the Gut Microbiome in Chemotherapy: A Clinical Review.

Increasing evidence suggests that the gut microbiome is associated with both cancer chemotherapy (CTX) outcomes and adverse events (AEs). This review examines the relationship between the gut microbiome and CTX as well as the impact of CTX on the gut microbiome. A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for "cancer" and "chemotherapy" and "microbiome/microbiota". The relevant literature was selected for use in this article. Seventeen studies were selected on participants with colorectal cancer (CRC; n=5), Acute Myeloid Leukemia (AML; n=3), Non-Hodgkin's lymphoma (n=2), breast cancer (BCa; n=1), lung cancer (n=1), ovarian cancer (n=1), liver cancer (n=1), and various other types of cancers (n=3). Seven studies assessed the relationship between the gut microbiome and CTX with faecal samples collected prior to (n=3) and following CTX (n=4) showing that the gut microbiome is associated with both CTX efficacy and toxicity. Ten other prospective studies assessed the impact of CTX during treatment and found that CTX modulates the gut microbiome of people with cancer and that dysbiosis induced by the CTX is related to AEs. CTX adversely impacts the gut microbiome, inducing dysbiosis and is associated with CTX outcomes and AEs. Current evidence provides insights into the gut microbiome for clinicians, cancer survivors and the general public. More research is required to better understand and modify the impact of CTX on the gut microbiome.

The Gut Microbiome and Gastrointestinal Toxicities in Pelvic Radiation Therapy: A Clinical Review.

BACKGROUND: Gastrointestinal (GI) toxicities are common adverse effects of pelvic radiotherapy (RT). Several recent studies revealed that toxicity of RT is associated with dysbiosis of the gut microbiome. METHOD: A literature search was conducted in electronic databases Medline, PubMed, and ScienceDirect, with search terms "microbiome and/or microbiota" and "radiotherapy (RT) and/or chemoradiation therapy (CRT)" and "cancer", and the relevant literature were selected for use in this article. RESULTS: Eight prospective cohort studies were selected for review with a total of 311 participants with a range of 15-134 participants within these studies. The selected studies were conducted in patients with gynaecological (n = 3), rectal (n = 2), or prostate cancers (n = 1), or patients with various types of malignancies (n = 2). Three studies reported that cancer patients had significantly lower alpha diversity compared with healthy controls. Seven studies found that lower alpha diversity and modulated gut microbiome were associated with GI toxicities during and after pelvic RT (n = 5) and CRT (n = 2), whereas one study found that beta diversity was related to a complete response following CRT. Two further studies reported that fatigue was associated with dysbiosis of the gut microbiome and low alpha diversity during and after RT, and with dysbiosis of the gut microbiome and diarrhoea, respectively. CONCLUSION: Gut microbiome profiles are associated with GI toxicities and have the potential to predict RT/CRT-induced toxicities and quality of life (QoL) in patients undergoing those treatments. Further robust randomized controlled trials (RCTs) are required to elucidate the effect of gut microbiome profiles on RT-related adverse effects and responses to RT.

Introducing Computed Tomography Simulation-Free and Electronic Patient-Reported Outcomes-Monitored Palliative Radiation Therapy into Routine Care: Clinical Outcomes and Implementation Experience.

PURPOSE: Our purpose was to report outcomes of a novel palliative radiation therapy protocol that omits computed tomography simulation and prospectively collects electronic patient-reported outcomes (ePROs). METHODS AND MATERIALS: Patients receiving extracranial, nonstereotactic, linear accelerator-based palliative radiation therapy who met inclusion criteria (no mask-based immobilization and a diagnostic computed tomography within 4 weeks) were eligible. Global pain was scored with the 11-point numerical pain rating scale (NPRS). Patients were coded as having osseous or soft tissue metastases and no/mild versus severe baseline pain (NPRS ≥ 5). Pain response at 4 weeks was measured according to the international consensus (no analgesia adjustment). Transition to ePRO questionnaires was completed in 3 phases. Initially, pain assessments were collected on paper for 11 months, then pilot ePROs for 1 month and then, after adjustments, revised ePROs from 1 year onwards. ePRO feasibility criteria were established with reference to the paper-based process and published evidence. RESULTS: Between May 2018 and November 2019, 542 consecutive patients were screened, of whom 163 were eligible (30%), and 160 patients were successfully treated. The proportion of patients eligible for the study improved from approximately 20% to 50% by study end. Routine care pain monitoring via ePROs was feasible. One hundred twenty-seven patients had a baseline NPRS recording. Ninety-five patients had osseous (61% severe pain) and 32 had soft tissue (25% severe pain) metastases. Eighty-four patients (66%) were assessable for pain response at 4 weeks. In the 41 patients with severe osseous pain, overall and complete pain response was 78% and 22%, respectively. CONCLUSIONS: By study completion, 50% of patients receiving palliative extracranial radiation therapy avoided simulation, streamlining the treatment process and maximizing patient convenience. Pain response for patients with severe pain from osseous lesions was equivalent to published evidence.

The Effects of Acupuncture on Cancer-Related Fatigue: Updated Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have identified fatigue as one of the major symptoms experienced during and after cancer treatment. However, there are limited options to manage cancer related fatigue (CRF) with pharmacological interventions. Several acupuncture studies suggested that acupuncture has a positive impact on CRF. This review aims to assess the evidence of acupuncture for the treatment of CRF. METHOD: Electronic database searches were conducted on 4 English databases (Medline, PubMed, Embase, and ScienceDirect). Search keywords were; "acupuncture" and "cancer," or "cancer related fatigue." Studies published as full text randomized controlled trials (RCTs) in English were included. Estimates of change in fatigue cores were pooled using a random effects meta-analysis where randomized comparisons were available for true acupuncture versus sham acupuncture and true acupuncture versus usual care. The quality of original papers were assessed using the Cochrane Collaboration's tool for assessing risk of bias (ROB). RESULTS: Nine RCTs were selected for review with a total of 809 participants and a range of 13 to 302 participants within the studies. Six RCTs reported significant improvement of CRF for the acupuncture intervention compared to the control groups. Pooled estimates suggest Brief Fatigue Inventory scores are 0.93 points lower 95% CI (-1.65, -0.20) in true acupuncture versus sham acupuncture and 2.12 points lower 95% C (-3.21, -1.04) in true acupuncture versus usual care. Six studies had low risk of bias (ROB) and 3 studies had a moderate ROB predominantly in blinding of participants, blinding of assessors and incomplete data outcomes. Among the 9 RCTs, 2 studies have reported the occurrence of minor adverse effects (spot bleeding and bruising) related to acupuncture treatment. No serious adverse reactions related to acupuncture were reported. CONCLUSION: The current literature review suggests that acupuncture has therapeutic potential in management of CRF for cancer survivors. Promotion of acupuncture in cancer care to manage CRF may improve the quality of life of cancer survivors.

Developing knowledge-based planning for gynaecological and rectal cancers: a clinical validation of RapidPlan™.

INTRODUCTION: To create and clinically validate knowledge-based planning (KBP) models for gynaecologic (GYN) and rectal cancer patients. Assessment of ecologic generalisability and predictive validity of conventional planning versus single calculation KBP was reviewed against practical metrics of planning time (PT) and radiation oncologist plan preference. METHOD: Study cohorts were 34 and 42 consecutively treated GYN and rectal cancer patients dosimetrically archived within the centre's research databank. For model training, structures and dose distributions from 22 and 32 GYN and rectal volumetric-modulated arc therapy (VMAT) plans were used in RapidPlan™. Prescription doses ranged from 45 to 60Gy in 25 fractions using a simultaneous integrated boost to 2-4 targets and up to 9 organ-at-risk volumes. For model validation, 12 GYN and 10 rectal were independent of the archive and a single pass KBP VMAT plan was created. Each plan was evaluated against the archived treated plan under blinded conditions for radiation oncologist preference using standard dosimetric quality parameters. RESULTS: All 22 plans generated in the KBP validation cohort met pre-set GYN and rectal cancer dosimetric quality metrics. Fifty per cent of GYN plans and eighty per cent of rectal plans were judged superior to the manually optimised plans. KBP reduced PT considerably for both tumour sites. CONCLUSION: Single pass KBP for GYN and rectal cancer patients produced clinically acceptable treatment plans which were non-inferior to conventionally optimised plans in 14 of 22 cases. Efficiencies captured by KBP will have predictable impacts on institutional workflows and resource allocation to facilitate adaptive planning.

Breast interest group faculty of radiation oncology: Australian and New Zealand patterns of practice survey on breast radiotherapy.

INTRODUCTION: This patterns of practice study was conducted on behalf of the RANZCR Breast Interest Group in order to document current radiotherapy practices for breast cancer in Australia and New Zealand. The survey identifies variations and highlights potential contentious aspects of radiotherapy management of breast cancer. METHODS: A fifty-eight question survey was disseminated via the Survey Monkey digital platform to 388 Radiation Oncologists in Australia and New Zealand. RESULTS: In total, 156 responses were received and collated. Areas of notable consensus among respondents included hypofractionation (77.3% of respondents would 'always' or 'sometimes' consider hypofractionation in the management of ductal carcinoma in-situ and 99.3% in early invasive breast cancer); margin status in early breast cancer (73.8% believe a clear inked margin is sufficient and does not require further surgery) and use of bolus in post-mastectomy radiotherapy (PMRT) (91.1% of participants use bolus in PMRT). Areas with a wider degree of variability amongst respondents included regional nodal irradiation and components of radiotherapy planning and delivery (examples include the technique used for delivery of boost and frequency of bolus application for PMRT). CONCLUSION: The results of these patterns of practice survey informs radiation oncologists in Australia and New Zealand of the current clinical practices being implemented by their peers. The survey identifies areas of consensus and contention, the latter of which may lead to a development of research trials and/or educational activities to address these areas of uncertainty.

Benchmarking clinical practice quality: an audit of ipsilateral breast tumor recurrence in patients managed for T1/T2 breast carcinoma.

AIM: Breast conserving surgery and adjuvant radiotherapy has equivalent oncological outcomes to mastectomy and is the standard of care for treatment of early-stage invasive breast cancer. Auditing is an essential component of ongoing quality assurance and clinical governance. It also serves to identify patient and tumor factors that have prognostic and therapeutic implications. The aim of this paper is to report on the clinical audit of treatment outcomes for patients undergoing adjuvant radiation treatment for early breast cancer at the Northern Sydney Cancer Care Centre. METHODS: A total of 1252 patients with T1/2 breast cancer received adjuvant radiation treatment between January 2003 and December 2010. Medical records, including the departmental database, were reviewed to extract pathological, treatment, patient and clinical details. RESULTS: Median follow-up was 54 months (mean 56.4 months). Sixty-six (5.27%) patients died from breast cancer, and 27 (2.16%) patients died from other disease. Twenty-three (1.84%) patients were alive with metastatic disease, 7 (0.56%) patients were alive following ipsilateral breast tumor recurrence and 7 (0.56%) patients were alive with nodal recurrence. 9 (0.72%) patients were alive with contralateral breast cancer. Documented rates of late toxicity were low: 6.8% of patients had grade 1 late toxicity and 1.6% of patients had grade 2-3 late toxicity. CONCLUSION: Our ipsilateral breast tumor recurrence rate of 0.56% is well within international standards, as is our toxicity rate. We propose that centralized data collection be implemented on a nation-wide level for breast cancer patients undergoing radiotherapy. Further research is planned to identify potential markers of radio-resistance, and allow tailoring of treatment technique to optimize oncological outcome.

A clip-based protocol for breast boost radiotherapy provides clear target visualisation and demonstrates significant volume reduction over time.

INTRODUCTION: The clinical target volume (CTV) for early stage breast cancer is difficult to clearly identify on planning computed tomography (CT) scans. Surgical clips inserted around the tumour bed should help to identify the CTV, particularly if the seroma has been reabsorbed, and enable tracking of CTV changes over time. METHODS: A surgical clip-based CTV delineation protocol was introduced. CTV visibility and its post-operative shrinkage pattern were assessed. The subjects were 27 early stage breast cancer patients receiving post-operative radiotherapy alone and 15 receiving post-operative chemotherapy followed by radiotherapy. The radiotherapy alone (RT/alone) group received a CT scan at median 25 days post-operatively (CT1rt) and another at 40 Gy, median 68 days (CT2rt). The chemotherapy/RT group (chemo/RT) received a CT scan at median 18 days post-operatively (CT1ch), a planning CT scan at median 126 days (CT2ch), and another at 40 Gy (CT3ch). RESULTS: There was no significant difference (P = 0.08) between the initial mean CTV for each cohort. The RT/alone cohort showed significant CTV volume reduction of 38.4% (P = 0.01) at 40 Gy. The Chemo/RT cohort had significantly reduced volumes between CT1ch: median 54 cm(3) (4-118) and CT2ch: median 16 cm(3), (2-99), (P = 0.01), but no significant volume reduction thereafter. CONCLUSION: Surgical clips enable localisation of the post-surgical seroma for radiotherapy targeting. Most seroma shrinkage occurs early, enabling CT treatment planning to take place at 7 weeks, which is within the 9 weeks recommended to limit disease recurrence.

Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index.

INTRODUCTION: We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. METHODS: Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. RESULTS: The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D 105% and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). CONCLUSION: Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.

A dosimetric comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large and small breast volumes.

Radiation therapy to the breast is a complex task, with many different techniques that can be employed to ensure adequate dose target coverage while minimizing doses to the organs at risk. This study compares the dose planning outcomes of 3 radiation treatment modalities, 3 dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and static tomotherapy, for left-sided whole-breast radiation treatment with a simultaneous integrated boost (SIB). Overall, 20 patients with left-sided breast cancer were separated into 2 cohorts, small and large, based on breast volume. Dose plans were produced for each patient using 3D-CRT, IMRT, and static tomotherapy. All patients were prescribed a dose of 45Gy in 20 fractions to the breast with an SIB of 56Gy in 20 fractions to the tumor bed and normalized so that D98% > 95% of the prescription dose. Dosimetric comparisons were made between the 3 modalities and the interaction of patient size. All 3 modalities offered adequate planning target volume (PTV) coverage with D98% > 95% and D2% < 107%. Static tomotherapy offered significantly improved (p = 0.006) dose homogeneity to the PTVboost eval (0.079 ± 0.011) and breast minus the SIB volume (BreastSIB) (p < 0.001, 0.15 ± 0.03) compared with the PTVboost eval (0.085 ± 0.008, 0.088 ± 0.12) and BreastSIB (0.22 ± 0.05, 0.23 ± 0.03) for IMRT and 3D-CRT, respectively. Static tomotherapy also offered statistically significant reductions (p < 0.001) in doses to the ipsilateral lung mean dose of 6.79 ± 2.11Gy compared with 7.75 ± 2.54Gy and 8.29 ± 2.76Gy for IMRT and 3D-CRT, respectively, and significantly (p < 0.001) reduced heart doses (mean = 2.83 ± 1.26Gy) compared to both IMRT and 3D-CRT (mean = 3.70 ± 1.44Gy and 3.91 ± 1.58Gy). Static tomotherapy is the dosimetrically superior modality for the whole breast with an SIB compared with IMRT and 3D-CRT. IMRT is superior to 3D-CRT in both PTV dose conformity and reduction of mean doses to the ipsilateral lung.

Tumor and normal tissue dosimetry changes during MR-guided pulsed-dose-rate (PDR) brachytherapy for cervical cancer.

BACKGROUND AND PURPOSE: To analyze systematic changes in tumor and normal tissue anatomy and dosimetry using serial MR imaging during pulsed dose rate brachytherapy (PDR BT) for cervical cancer. MATERIAL AND METHODS: Forty-three patients with cervical cancer underwent MR-guided PDR BT using an intrauterine applicator alone after external beam radiotherapy. MR imaging was repeated on days 2 and 3 of treatment and the day 1 plan was applied to the re-contoured volumes. RESULTS: The mean uterine volume and mean HR CTV increased during treatment. This resulted in a decrease in the mean HR CTV D90 relative to the day 1 planned dose. There was no change in the mean bladder volume during treatment but the mean rectal volume increased. This correlated with an increase in the mean rectal dose. There were four local recurrences. There was no apparent relationship between either the planned or the delivered HR CTV D90 and local recurrence. There was only one case of late bladder toxicity but nine patients developed late rectal toxicity. The cumulative rectal dose during treatment was a better predictor of late rectal toxicity than the planned dose. CONCLUSIONS: Significant changes in tumor and normal tissue anatomy and dosimetry can occur during PDR BT and should be tracked and corrected using serial imaging and plan adaptation, especially when the day 1 tumor or normal tissue doses are close to the planning constraints.

Technological advances in radiotherapy for cervical cancer.

PURPOSE OF REVIEW: To discuss the important technological advances that have taken place in the planning and delivery of both external beam radiotherapy and brachytherapy for patients with locally advanced cervical cancer, and the implications for improved clinical outcomes. RECENT FINDINGS: Technological advances in external beam radiation treatment and brachytherapy for patients with cervical cancer allow more precise targeting of tumour and relative sparing of surrounding normal organs and tissues. Early evidence is emerging to indicate that these advances will translate into improvements in tumour control and reduced side effects. However, there are patient, tumour and treatment-related factors that can detract from these benefits. Foremost among these is complex, unpredictable and sometimes dramatic internal tumour and normal organ motion during treatment. The focus of current research and clinical development is on tracking internal anatomic change in individual patients and adapting treatment plans as required to assure that optimal tumour coverage and normal tissue sparing is maintained at all times. The success of this approach will depend on clear definitions of target volumes, high resolution daily soft tissue imaging, and new software tools for rapid contouring, treatment planning and quality assurance. SUMMARY: Radiation treatment of locally advanced cervical cancer is evolving rapidly, driven by advances in technology, towards more individualized patient care that has the potential to substantially improve clinical outcomes.