Including Intensity-modulated Radiotherapy Research Articles

A retrospective analysis of tislelizumab and GP regimen neoadjuvant therapy followed by concurrent chemoradiotherapy plus nimotuzumab in patients with high-risk nasopharyngeal carcinoma.

e18060 Background: Efficacy of nasopharyngeal carcinoma (NPC) with T4 or N3 remains unsatisfactory due to high-risk of distant metastasis or recurrence, indicating the need of more comprehensive treatment. We aim to analysis the efficacy and safety of tislelizumab and GP regimen in combination with neoadjuvant therapy and concurrent chemoradiotherapy (CCRT) plus nimotuzumab in patients with high-risk NPC. Methods: Our team conducted a retrospective analysis of 44 adult patients with high-risk locally advanced (T4 or N3; M0) nasopharyngeal carcinoma between March 2021 and January 2022, the median follow-up time was 599 days. The patients had received neoadjuvant chemotherapy (gemcitabine,1000 mg/m2, days 1 and 8, cisplatin,80 mg/m2, day 1), and tislelizumab (200mg) on day 1 every 3 weeks for 4 cycles followed by chemoradiotherapy including intensity modulated radiotherapy (IMRT), lobaplatin and nimotuzumab. Lobaplatin was intravenously administered at a dose of 30 mg/m2 on days 1 and 22. Nimotuzumab was intravenously administered at a dose of 200 mg on day 1 every week for 6 weeks. All patients underwent response assessments during neoadjuvant therapy, chemoradiotherapy and follow-up at regular intervals. Results: 44 patients were identified with the median age being 50y(24y-70y). At neoadjuvant treatment period, 44 patients completed 170 cycles of the combination of tislelizumab and GP regimen. During concurrent chemo-radiotherapy period, 42 (95.45%) of 44 patients completed 6 weeks of nimotuzumab treatment and 41 (93.18%) of 44 patients completed 2 cycles of lobaplatin treatment. Overall, 20 patients (45.5%) had a complete response, and 24 (54.5%) had a partial response after neoadjuvant therapy before the start of chemoradiotherapy. At 3 months and 6 months after radiotherapy, 90.9% (40 of 44) and 97.7% (43 of 44) of the patients had a complete response. 42 of the 44 patients were alive (95.5%). 3 events of recurrence(1) or death(2) were recorded. 19 (43.2%) of 44 patients had grade 3-4 treatment-related adverse events, and grade 3-4 immune-related adverse events(irAE) was recorded in 3 patients (6.8%) in the entire treatment. Grade 3-4 irAEs were rash(2) and hypothyroidism(1). Conclusions: Neoadjuvant therapy with tislelizumab and GP regimen followed by concurrent chemoradiotherapy plus nimotuzumab seems to have promising efficacy, lower toxic effects and better treatment compliance, which is a new treatment strategy for high-risk NPC.

Standard but Not Equal: Disparities in Advanced Radiotherapy Techniques for Head and Neck Cancer in the United States

<h3>Purpose/Objective(s)</h3> Advanced radiotherapy techniques (ART), including intensity-modulated radiotherapy (IMRT) and proton beam therapy (PBT), offer enhanced conformality, can reduce acute and late toxicities from radiotherapy for head and neck cancers (HNC), and are considered standard-of-care by consensus guidelines. This study aims to characterize implementation of ART and corresponding patterns of care in the United States since 2004. <h3>Materials/Methods</h3> Data for patients treated with external beam radiotherapy for primary HNC (any histology) were extracted from the National Cancer Database (2004-2017). Cases with metastatic disease and early stage glottic larynx cancer (Tis-T2,N0) were excluded. ART was defined as radiotherapy delivery with either IMRT or PBT, while non-ART encompassed 2D or 3D-conformal techniques. Sociodemographic, facility-specific, and clinical associations with receipt of ART were assessed by logistic regression. <h3>Results</h3> 177,373 patients with HNC were eligible for analysis; 94.2% received ART (IMRT: 93.3%, PBT: 0.9%), and 5.8% received non-ART. ART utilization increased substantially from 3,317 (78.0%) in 2004 to 14,088 (96.0%) in 2012 (p<0.001), largely driven by adoption of IMRT (77.0% to 95.7%). Use of ART increased slightly between 2012 and 2017 (96.0% to 96.9%; p<0.001), driven by growth in PBT (0.3% to 2.7%; p<0.001). On multivariable logistic regression, black patients were less likely to receive ART (OR 0.87; 95%CI 0.80-0.94), as were older patients (continuous OR 0.95; 95%CI 0.93-0.96), the uninsured (OR 0.70; 95%CI 0.63-0.78), and those with Medicaid (OR 0.80; 95%CI 0.74-0.87). Patients undergoing care at treatment facilities in the Northeast or Midwest, of non-academic affiliation, and with lower HNC volume were also less likely to receive ART. Census-tract level measures of income and educational attainment were directly correlated with receipt of ART. Likewise, nasopharyngeal or oropharyngeal primary site, advanced T- or N-classification, and receipt of chemotherapy or surgery were each independently associated with receipt of ART. <h3>Conclusion</h3> ART utilization has increased since the early 2000's, driven initially by IMRT and more recently by PBT. Despite the near-ubiquity of ART today, we identified racial, socioeconomic, and geographic disparities in their adoption, potentially exposing disadvantaged patients to preventable toxicity and quality-of-life insults from non-ART.

Speech and Swallowing Outcomes Following Surgical Resection with Immediate Free Tissue Transfer Reconstruction for Advanced Osteoradionecrosis of the Mandible Following Radiation Treatment for Head and Neck Cancer

Despite recent advances in the radiation techniques used for the treatment of head and neck cancer (HNC) including intensity-modulated radiotherapy (IMRT), mandibular osteoradionecrosis (ORN) remains a significant complication. Advanced stage ORN is managed surgically with resection and immediate free tissue transfer reconstruction. An evaluation of the functional speech and swallowing outcomes was undertaken for patients undergoing surgical management of advanced ORN. We retrospectively reviewed consecutive patients, at a single, tertiary cancer centre, who underwent surgical resection for advanced Notani grade III ORN. Outcomes investigated included use and duration of tracheostomy and swallowing and speech status using Performance Status Scale for Head and Neck Cancer Normalcy of Diet (PSS-NOD) and Understandability of Speech (PSS-Speech) at baseline and 3 months following surgery. Ten patients underwent surgical resection with free tissue transfer reconstruction between January 2014 and December 2019. Two patients required supplemental nutrition via a gastrostomy at three months post surgery. As per the PSS-NOD data half of the patients’ (n = 5) diet remained stable (n = 2) or improved (n = 3) and half of the participants experienced a decline in diet (n = 5). The majority of patients had no speech difficulties at baseline (n = 8). The majority of patients’ speech remained stable (n = 8) with two patients experiencing a deterioration in speech clarity following surgery. Well-designed studies with robust, sensitive multidimensional dysphagia and communication assessments are required to fully understand the impact of surgical management of advanced ORN using resection with free tissue transfer reconstruction.

The impact of modern radiotherapy on radiation-induced late sequelae: Focus on early-stage mediastinal classical Hodgkin Lymphoma. A critical review by the Young Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

The historically feared radiation-induced secondary cancers and cardiac toxicities observed among mediastinal classical Hodgkin Lymphoma (cHL) patients may still negatively burden the benefit of radiotherapy among long-term survivors. Modern radiotherapy (RT) delivery techniques, including intensity-modulated RT (IMRT) and deep inspiration breath-hold (DIBH) solutions, are drastically changing this scenario. Results of a literature overview are reported and discussed in this paper. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of organs-at-risk dose-volume metrics linked with radiation-induced toxicities in cHL patients. The scenario of early-stage cHL presents long-life expectancies, thus the goal of treatment should aim at maintaining high cure rates and limiting the onset of late complications. Further evaluations of dosimetric measures and clinical outcomes are warranted to identify patients at higher risk to target treatment tailoring.

Cost-effectiveness analysis of advanced radiotherapy techniques for post-mastectomy breast cancer patients

BackgroundPrior cost-effectiveness studies of post-mastectomy radiotherapy (PMRT) only compared conventional radiotherapy versus no radiotherapy and only considered tumor control. The goal of this study was to perform cost-effectiveness analyses of standard of care (SOC) and advanced PMRT techniques including intensity-modulated radiotherapy (IMRT), standard volumetric modulated arc therapy (STD-VMAT), non-coplanar VMAT (NC-VMAT), multiple arc VMAT (MA-VMAT), Tomotherapy (TOMO), mixed beam therapy (MIXED), and intensity-modulated proton therapy (IMPT).MethodsUsing a Markov model, we estimated the cost-effectiveness of various techniques over 15 years. A cohort of women (55-year-old) was simulated in the model, and radiogenic side effects were considered. Transition probabilities, utilities, and costs for each health state were obtained from literature and Medicare data. Model outcomes include quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER).ResultsFor the patient cohort, STD-VMAT has an ICER of $32,617/QALY relative to SOC; TOMO is dominated by STD-VMAT; IMRT has an ICER of $19,081/QALY relative to STD-VMAT; NC-VMAT, MA-VMAT, MIXED are dominated by IMRT; IMPT has an ICER of $151,741/QALY relative to IMRT. One-way analysis shows that the probability of cardiac toxicity has the most significant impact on the model outcomes. The probability sensitivity analyses show that all advanced PMRT techniques are more cost-effective than SOC at a willingness-to-pay (WTP) threshold of $100,000/QALY, while almost none of the advanced techniques is more cost-effective than SOC at a WTP threshold of $50,000/QALY.ConclusionAdvanced PMRT techniques are more cost-effective for breast cancer patients at a WTP threshold of $100,000/QALY, and IMRT might be a cost-effective option for PMRT patients.

Effect of dose constraint on the thyroid gland during locoregional intensity-modulated radiotherapy in breast cancer patients.

The aim of the present study was to compare radiation dose received by thyroid gland using different radiotherapy (RT) techniques with or without thyroid dose constraint (DC) for breast cancer patients. Computerized tomography (CT) image sets for 10 patients with breast cancer were selected. All patients were treated originally with opposite tangential field‐in field (FinF) for the chest wall and anteroposterior fields for the ipsilateral supraclavicular field. The thyroid gland was not contoured on the CT images at the time of the original scheduled treatment. Four new treatment plans were created for each patient, including intensity‐modulated radiotherapy (IMRT) and helical tomotherapy (HT) plans with thyroid DC exclusion and inclusion (IMRTDC(−), IMRTDC(+), HTDC(−), and HTDC(+), respectively). Thyroid DCs were used to create acceptable dose limits to avoid hypothyroidism as follows: percentage of thyroid volume exceeding 30 Gy less than 50% (V 30 < 50%) and mean dose of thyroid (TDmean) ≤ 21 Gy. Dose‐volume histograms (DVHs) for TDmean and percentages of thyroid volume exceeding 10, 20, 30, 40, and 50 Gy (V 10, V 20, V 30, V 40, and V 50, respectively) were also analyzed. The Dmean of the FinF, IMRTDC(−), HTDC(−), IMRTDC(+) and HTDC(+) plans were 30.56 ± 5.38 Gy, 25.56 ± 6.66 Gy, 27.48 ± 4.16 Gy, 18.57 ± 2.14 Gy, and 17.34 ± 2.70 Gy, respectively. Median V30 values were 55%, 33%, 36%, 18%, and 17%, for FinF, IMRTDC(−), HTDC(−), IMRTDC(+), and HTDC(+), respectively. Differences between treatment plans with or without DC with respect to D mean and V 30 values were statistically significant (P < 0.05). When thyroid DC during breast cancer RT was applied to IMRT and HT, the TDmean and V 30 values significantly decreased. Therefore, recognition of the thyroid as an organ at risk (OAR) and the use of DCs during IMRT and HT planning to minimize radiation dose and thyroid volume exposure are recommended.

846P - Patterns of therapy in pelvic lymph node positive prostate cancer in Europe and Asia: A real-world data analysis

Background: Treatment for node positive prostate cancer can vary from palliation to radical therapy. Guidance for N1 prostate cancer is unclear but evidence supports a multimodal approach including radical radiotherapy, hormonal manipulation and possible surgery while a survival benefit for neoadjuvant docetaxel has been demonstrated. Recent improvements in diagnostic techniques and technical advances in radiation therapy including intensity modulated radiotherapy (IMRT) which is capable of delivering a radical dose of radiation to pelvic nodes within acceptable toxicity profiles are anticipated to result in an increased use of radiation in this patient population. This study assesses changes in treatment modality for N1 prostate cancer over time to reflect real world practice. Methods: Patient data from 17,695 prostate cancer cases taken from a cross-sectional survey of physicians in France, Germany, Italy, Spain, UK, China, Japan and S. Korea between Jan 1997 – Dec 2016 was reviewed. Patients with non-metastatic, node positive cancer were included for analysis. Any exposure to any of three therapy types (systemic, radiation, surgery) prior to recurrence. Results: 2542 patients were included in the analysis. Over the time studied, the use of surgery has decreased (from 36% in pre 2009 to 16% in 2016) and initially, this decline was matched by a rise in the use of systemic therapy alone (37% to 51%). Since 2011 systemic therapy alone has reduced to 40%. In the same time period, there has been an increase in the use of radiation (with or without systemic therapy) to treat node positive prostate cancer (15% to 29%). The average increase in radiotherapy use across European countries was 11% (range Italy 2% - Spain 19%). A group of patients receiving combined surgery, radiation and systemic therapy comprise 11% of all cases, a figure that does not vary over time. Conclusions: These data have demonstrated an international change in the management of node positive prostate cancer with decreasing use of surgery and increasing use of radiation. Although initially rising, the recent decline in the use of lone systemic therapy is likely to represent an increasing view that N1 prostate cancer is no longer a definitively palliative diagnosis. Legal entity responsible for the study: IQVIA. Funding: IQVIA. Disclosure: I. Wong: Honoraria: Janssen, Sanofi Aventis. H. Payne: Honoraria, advisory boards, travel expenses, consultant: AstraZeneca, Astellas, Janssen, Sanofi Aventis, Takeda, Amgen, Ipsen, Ferring, Sandoz and Novartis; Work support: UCLH/UCL Comprehensive Biomedical Research Centre. All other authors have declared no conflicts of interest.

Robust optimization in lung treatment plans accounting for geometric uncertainty.

Robust optimization generates scenario‐based plans by a minimax optimization method to find optimal scenario for the trade‐off between target coverage robustness and organ‐at‐risk (OAR) sparing. In this study, 20 lung cancer patients with tumors located at various anatomical regions within the lungs were selected and robust optimization photon treatment plans including intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were generated. The plan robustness was analyzed using perturbed doses with setup error boundary of ±3 mm in anterior/posterior (AP), ±3 mm in left/right (LR), and ±5 mm in inferior/superior (IS) directions from isocenter. Perturbed doses for D99, D98, and D95 were computed from six shifted isocenter plans to evaluate plan robustness. Dosimetric study was performed to compare the internal target volume‐based robust optimization plans (ITV‐IMRT and ITV‐VMAT) and conventional PTV margin‐based plans (PTV‐IMRT and PTV‐VMAT). The dosimetric comparison parameters were: ITV target mean dose (Dmean), R95(D95/Dprescription), Paddick's conformity index (CI), homogeneity index (HI), monitor unit (MU), and OAR doses including lung (Dmean, V20 Gy and V15 Gy), chest wall, heart, esophagus, and maximum cord doses. A comparison of optimization results showed the robust optimization plan had better ITV dose coverage, better CI, worse HI, and lower OAR doses than conventional PTV margin‐based plans. Plan robustness evaluation showed that the perturbed doses of D99, D98, and D95 were all satisfied at least 99% of the ITV to received 95% of prescription doses. It was also observed that PTV margin‐based plans had higher MU than robust optimization plans. The results also showed robust optimization can generate plans that offer increased OAR sparing, especially for normal lungs and OARs near or abutting the target. Weak correlation was found between normal lung dose and target size, and no other correlation was observed in this study.

Definite chemoradiotherapy is a competent treatment option in FIGO stage IB2 cervical cancer compared with radical surgery +/- neoadjuvant chemotherapy.

To compare the treatment outcomes of different treatment modalities for International Federation of Gynecology and Obstetrics (FIGO) stage IB2 cervical cancer. From January 2002 to July 2016, 91 patients with FIGO stage IB2 squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the cervix were enrolled. All of them received one of the following treatment modalities, including intensity-modulated radiotherapy (IMRT) with concurrent platinum-based chemotherapy (CCRT group, n=27), radical surgery with or without adjuvant treatment (RH group, n=25), or neoadjuvant chemotherapy followed by radical surgery with or without adjuvant treatment (NACT group, n=39). Overall survival (OS), disease free survival (DFS), loco-regional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were compared among the three different groups. The median follow up durations were 63.3 months for the CCRT group, 83.5 months for the NACT group, and 89.8 months for the RH group, respectively. The 5-year OS, DFS, LRFFS and DMFS for CCRT group vs. NACT group vs. RH group were 80.1% vs. 94.1% vs. 93.8% (p=0.197), 79.5% vs. 79.3% vs. 91.0% (p=0.401), 88.1% vs. 81.8% vs. 95.8% (p=0.253), and 83.3% vs. 88.8% vs. 95.2% (p=0.422). No significant prognostic factor was found in OS. Age>48 was significant in predicting poor DFS and DMFS. The non-squamous cell carcinoma was a significant predictor of poor DFS, LRFFS and DMFS. CCRT is a feasible therapeutic option with acceptable acute and chronic treatment-related toxicities for patients who cannot tolerate radical surgery or neoadjuvant chemotherapy.

Radiation Treatment in Women with Ovarian Cancer: Past, Present, and Future.

Ovarian cancer is the most lethal of the gynecologic cancers, with 5-year survival rates less than 50%. Most women present with advanced stage disease as the pattern of spread is typically with dissemination of malignancy throughout the peritoneal cavity prior to development of any symptoms. Prior to the advent of platinum-based chemotherapy, radiotherapy was used as adjuvant therapy to sterilize micrometastatic disease. The evolution of radiotherapy is detailed in this review, which establishes radiotherapy as an effective therapy for women with micrometastatic disease in the peritoneal cavity after surgery, ovarian clear cell carcinoma, focal metastatic disease, and for palliation of advanced disease. However, with older techniques, the toxicity of whole abdominal radiotherapy and the advancement of systemic therapies have limited the use of radiotherapy in this disease. With newer radiotherapy techniques, including intensity-modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and low-dose hyperfractionation in combination with targeted agents, radiotherapy could be reconsidered as part of the standard management for this deadly disease.

Technical advances in external radiotherapy for hepatocellular carcinoma.

Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy.

Palliative Radiotherapy: Current Status and Future Directions

For nearly 100 years, palliative radiotherapy has been a time-efficient, effective treatment for patients with metastatic or advanced cancer in any area where local tumors are causing symptoms. Short courses including a single fraction of radiotherapy may be effective for symptom relief with minimal side effects and maximization of convenience for patient and family. With recent advances in imaging, surgery, and other local therapies as well as systemic cancer therapies, palliative radiotherapy has been used frequently in patients who may not yet have symptoms of advanced or metastatic cancer. In this setting, more prolonged radiotherapy courses and advanced radiotherapy techniques including intensity-modulated radiotherapy (IMRT) or stereotactic radiotherapy (SRT) may be useful in obtaining local control and durable palliative responses. This review will explore the use of radiotherapy across the spectrum of patients with advanced and metastatic cancer and delineate an updated, rational approach for the use of palliative radiotherapy that incorporates symptoms, prognosis, and other factors into the delivery of palliative radiotherapy.

Abstract 4536: Combination external beam and internal radiation via 131I-CLR1404 in the treatment of head and neck squamous cell carcinoma xenografts.

Abstract Radiotherapy (RT) is a central treatment modality for head and neck cancer (HNC). However, optimal outcome is commonly limited by the radiation tolerance of adjacent normal tissue structures. Radiation is sometimes valuable in the setting of locoregional tumor recurrence, however the risk of significant normal tissue toxicity is substantial with repeat irradiation and can have a profound adverse impact on patient quality of life. Although technical advances including intensity modulated radiotherapy (IMRT) can reduce normal tissue effects, the problem of repeat exposure of normal tissues to radiation is frequently limiting. The radiolabeled drug 124/131I-CLR1404 is a phospholipid ether analogue (PLE) that accumulates preferentially within malignant tumors and enables internal delivery of radiation. This allows a combination of external and internal radiotherapy delivery with a goal of improving treatment outcome without enhanced normal tissue toxicities. In this study, we characterized the ability of 131I-CLR1404 to augment RT response using xenografted mice harboring human squamous cell carcinomas (SCC). We determined tumor growth delay as well as tumor and normal tissue dose distribution of 131I-CLR-1404 via Monte Carlo simulation using PET data generated with 124I-CLR1404 imaging. Tumor growth delay was extended by 15.5 days using combined 3.7MBq 131I-CLR1404 and RT compared to RT or 131I-CLR1404 alone. In combination therapy, single dose administration of 7.4 MBq 131I-CLR1404 as well as split dosing with 2 x 3.7 MBq separated by one week showed the same additional growth delay of 27 days compared to single dose of 3.7 MBq. Monitoring drug distribution via PET/CT showed high tumor selectivity with a tumor-to-liver ratio of 6.2±0.65 and a tumor-to-muscle ratio of 6.7±0.21. These data illustrate the tumor selectivity of the CLR1404 PLE delivery platform as well as augmentation of tumor response with combined RT and 131I-CLR1404 treatment. De-intensification of external beam radiation dose, with attendant reduction in normal tissue toxicities so common in HNC patients represents a central objective to be tested in controlled clinical trials with the ultimate goal of improving treatment outcome and quality of life for HNC patients. Citation Format: Jarob Saker, Eric Armstrong, Bryan Bednarz, Mohammed Farhoud, Abigail Besemer, Jamey Weichert, Paul Harari. Combination external beam and internal radiation via 131I-CLR1404 in the treatment of head and neck squamous cell carcinoma xenografts. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4536. doi:10.1158/1538-7445.AM2013-4536

Pelvic insufficiency fractures in patients with cervical and endometrial cancer treated with postoperative pelvic radiation

ObjectiveThere is an increased awareness of pelvic insufficiency fractures (PIF) as a potential morbidity of pelvic radiotherapy (RT). The purpose of this study was to determine the incidence of PIF and assess prognostic factors, including intensity-modulated RT (IMRT), in gynecologic oncology patients treated with postoperative pelvic RT. MethodsWe performed a retrospective review of all patients with endometrial or cervical carcinoma who received postoperative pelvic RT at our institution during 2000–2008. Patients who received definitive or palliative RT were excluded. ResultsA total of 222 patients were identified, of whom 11 (5%) developed PIF at a median time of 11.5months (range, 5.5–87.3months) from RT completion. The 5-year actuarial rate was 5.1% (95% CI 3.3–6.9). In patients with osteoporosis, the 5-year rate was 15.6% compared with 2.9% for those without (P=0.01). Similarly, patients who were on prior hormone-replacement therapy (HRT) had a higher rate (14.8% vs 4.1%, P=0.009). The median body-mass index (BMI) for patients who developed PIF was significantly lower than those who didn't (25.9 vs 27.2, P=0.016). The rate of PIF was 4.9% whether patients received IMRT or conventional RT. ConclusionsThe 5-year risk of PIF for postoperative pelvic RT in cervical and endometrial cancer is 5.1%. Women with history of osteoporosis, prior HRT, or low BMI need to be counseled about the risk of PIF. The use of IMRT did not decrease PIF, but further studies are needed to determine if a dose/volume relationship exists between RT and PIF.

What is New in Rhabdomyosarcoma Management in Children?

Optimal management of rhabdomyosarcoma requires establishing the correct pathologic diagnosis, histologic sub-type, primary site, extent of disease (Stage), and extent of resection (Group). Based on these features, cooperative groups in North America and Europe have defined risk-adapted treatments that include surgery, chemotherapy, and usually radiotherapy. This article focuses on recent findings that can impact or have already impacted rhabdomyosarcoma treatment guidelines and highlights controversies that should be addressed in order to improve outcome for children with rhabdomyosarcoma. Rhabdomyosarcoma is currently sub-classified in children based on histology into the favorable embryonal/botryoid/spindle cell types and the unfavorable alveolar form. Risk group assignment depends in part on histologic sub-type. Alveolar rhabdomyosarcoma is sometimes associated with chromosomal translocations, which impact clinical behavior. An important ongoing debate is whether molecular diagnostic tools to identify chromosomal translocations and/or define gene expression profiles should be used to sub-classify rhabdomyosarcoma rather than histology. Clinical trials continue to evaluate retrospective as well as prospective cohorts in order to carefully determine the impact of histology versus biologic features on outcome in the context of specific therapeutic regimens. Most rhabdomyosarcoma recurrences involve the primary site or adjacent region. Cooperative groups continue to investigate new approaches to local control in order to reduce local recurrences and sequelae associated with local therapy. Delaying primary resection until after chemotherapy has started appears to increase the number of tumors that can be completely resected with acceptable morbidity in some primary sites. Radiation dose reductions following delayed primary resection have been investigated. Although outcomes appear similar to the conventional approach of full-dose radiotherapy without delayed primary resection, long-term effects of the two approaches have not been rigorously compared. Early evidence suggests that newer methods of delivering radiotherapy, including intensity-modulated radiotherapy (IMRT), proton beam radiotherapy, and brachytherapy maintain efficacy but may reduce long-term sequelae compared with 3-dimensional conformal radiotherapy. Chemotherapy regimens defined by the cooperative groups vary by risk group. The most commonly used regimens include vincristine and dactinomycin in combination with an alkylating agent, either cyclophosphamide or ifosfamide. In order to improve outcomes, recent clinical trials have introduced new chemotherapeutic agents (e.g. topotecan, carboplatin, or epirubicin) into the treatment regimens. However, outcomes have not been significantly impacted. Novel chemotherapy administration schedules have been tested in patients with metastatic rhabdomyosarcoma, including interval compressed dosing or maintenance therapy, and may be promising. Molecularly targeted agents are currently under investigation in combination with chemotherapy for patients with recurrent or metastatic rhabdomyosarcoma. It is hoped that these novel agents will benefit all patients with rhabdomyosarcoma in the future.

Radiation treatment parameters for re-irradiation of malignant glioma

Most patients with malignant glioma ultimately fail locally or loco-regionally after the first treatment, with re-irradiation being a reasonable treatment option. However, only limited data are presently available allowing for a precise selection of patients suitable for re-treatment with regard to safety and efficacy. Using the department database, 39patients with a second course of radiation were identified. Doses to gross tumor volume (GTV), planning target volume (PTV), and relevant organs at risk (OARs; brainstem, optic chiasm, optic nerves, brain) were retrospectively analyzed and correlated to outcome parameters. Relevant treatment parameters including D(max), D(min), D(mean), and volume (ml) were obtained. Equivalent uniform dose (EUD) values were calculated for the tumor and OARs. To address the issue of radiation necrosis/leukoencephalopathy posttherapeutic MRI images were routinely examined every 3months. Median follow-up was 147days. The time interval between first and second irradiation was regularly greater than 6months. Median EUDs to the OARs were 11.9Gy (range 0.7-27.4Gy) to the optic chiasm, 17.6Gy (range 0.7-43.0Gy) to the brainstem, 4.9/2.1Gy (range 0.3-24.5Gy) to the right/left optic nerve, and 29.4Gy (range 25.2-32.5Gy) to the brain. No correlation between treated volume and survival was observed. Cold spots and dose did not correlate with survival. Re-irradiated volumes were treated with on average lower doses if they were larger and vice versa. In general, re-irradiation is a safe and feasible re-treatment option. No relevant toxicity was observed after re-irradiation in our patient cohort during follow-up. In this regard, this analysis provides baseline data for the selection of putative patients. EUD values are derived and may serve as reference for further studies, including intensity-modulated radiotherapy (IMRT) protocols.

Determination of target volumes in radiotherapy and the implications of technological advances: a literature review

AbstractThis study assesses the influence of new techniques and technologies in radiotherapy on the derivation and applicability of the margins currently used for treatment planning. The validity of the continued use of the recommendations of International Commission on Radiation Units and Measurements (ICRU) and other recommendations as a result of the additional information derived from these emerging techniques is also reviewed. The ICRU formulations still remain fundamental in the derivation of target volumes in radiotherapy; however, revisions to these have been recommended through various experimental and modelling techniques leading to the publication of various margin recipes. These recipes are used for margin definitions in new radiotherapy techniques including intensity-modulated radiotherapy (IMRT). The use of image-guided radiotherapy (IGRT) techniques leads to the reduction in organ motion uncertainties and setup errors, allowing for the adjustment of margins and treatment plans as well as dose escalation. Clinical trials are still needed to validate most of the new techniques in radiotherapy, particularly in IGRT techniques leading to adaptive radiotherapy. It is recommended that well devised clinical trials should be conducted to investigate fully the efficacy of these new techniques, particularly in radiotherapy image guidance and adaptive radiotherapy. Such trials would validate any recommendations regarding the current clinical margins and impact on their continued clinical use.

Uncertainty of Calculated Risk Estimates for Secondary Malignancies After Radiotherapy

The significance of risk estimates for fatal secondary malignancies caused by out-of-field radiation exposure remains unresolved because the uncertainty in calculated risk estimates has not been established. This work examines the uncertainty in absolute risk estimates and in the ratio of risk estimates between different treatment modalities. Clinically reasonable out-of-field doses and calculated risk estimates were taken from the literature for several prostate treatment modalities, including intensity-modulated radiotherapy (IMRT), and were recalculated using the most recent risk model. The uncertainties in this risk model and uncertainties in the linearity of the dose-response model were considered in generating 90% confidence intervals for the uncertainty in the absolute risk estimates and in the ratio of the risk estimates. The absolute risk estimates of fatal secondary malignancy were associated with very large uncertainties, which precluded distinctions between the risks associated with the different treatment modalities considered. However, a much smaller confidence interval exists for the ratio of risk estimates, and this ratio between different treatment modalities may be statistically significant when there is an effective dose equivalent difference of at least 50%. Such a difference may exist between clinically reasonable treatment options, including 6-MV IMRT versus 18-MV IMRT for prostate therapy. The ratio of the risk between different treatment modalities may be significantly different. Consequently risk models and associated risk estimates may be useful and meaningful for evaluating different treatment options. The calculated risk of secondary malignancy should be considered in the selection of an optimal treatment plan.

Radiosurgery of functioning pituitary adenomas: Comparison of different treatment techniques including dynamic and conformal arcs, shaped beams, and IMRT

Purpose: Evaluation of different techniques including intensity-modulated radiotherapy (IMRT) for stereotactic radiosurgery (SRS) of pituitary adenoma (PA). Methods and Materials: Between January 2003 and February 2005, 152 SRS procedures were performed. Ten patients with PA were compared: conformal vs. dynamic arc treatment with micromultileaf collimator (mMLC) vs. circular collimators vs. 8–10 conformal static mMLC beams with and without IMRT. Prescribed total dose: 18 Gy (90%). Constraints: D max optic chiasm 10Gy temporal lobe 10Gy temporal lobe. Results: For the end point "improvement in coverage," an advantage with IMRT was noted for 5 of 10 patients as compared with the dynamic arc approach. Volume treated >18 Gy outside the planning target volume was lowest in 9 of 10 patients after IMRT; 1 patient achieved better conformity with circular collimators. As for Vol 10Gy temporal lobe, an advantage was depicted for 1 of 10 patients with IMRT, the other techniques appearing equally effective in shielding the temporal lobe. With all techniques Vol 10 Gy temporal lobe was max optic chiasm Conclusions: Novalis-based radiosurgery using dynamic arc treatment with mMLC is considered a safe and appropriate approach for SRS of PA.