Yasemin Bolukbasi

Intensity-Modulated Radiotherapy versus 3-Dimensional Conformal Radiotherapy Strategies for Locally Advanced Non-Small-Cell Lung Cancer

Chemoradiotherapy is the current standard of care in patients with advanced inoperable stage IIIA or IIIB non-small cell lung cancer (NSCLC). Three-dimensional radiotherapy (3DCRT) has been a trusted method for a long time and has well-known drawbacks, most of which could be improved by Intensity Modulated Radiotherapy (IMRT). IMRT is not currently the standard treatment of locally advanced NSCLC, but almost all patients could benefit to a degree in organ at risk sparing, dose coverage conformality, or dose escalation. The most critical step for a radiation oncology department is to strictly evaluate its own technical and physical capabilities to determine the ability of IMRT to deliver an optimal treatment plan. This includes calculating the internal tumor motion (ideally 4DCT or equivalent techniques), treatment planning software with an up-to-date heterogeneity correction algorithm, and daily image guidance. It is crucial to optimise and individualise the therapeutic ratio for each patient during the decision of 3DCRT versus IMRT. The current literature rationalises the increasing use of IMRT, including 4D imaging plus PET/CT, and encourages the applicable knowledge-based and individualised dose escalation using advanced daily image-guided radiotherapy.

Reproducible deep-inspiration breath-hold irradiation with forward intensity-modulated radiotherapy for left-sided breast cancer significantly reduces cardiac radiation exposure compared to inverse intensity-modulated radiotherapy.

AIMS AND BACKGROUNDnTo investigate the objective utility of our clinical routine of reproducible deep-inspiration breath-hold irradiation for left-sided breast cancer patients on reducing cardiac exposure.nnnMETHODS AND STUDY DESIGNnFree-breathing and reproducible deep-inspiration breath-hold scans were evaluated for our 10 consecutive left-sided breast cancer patients treated with reproducible deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated radiotherapy plans were generated for each computed tomography dataset.nnnRESULTSnReproducible deep-inspiration breath-hold plans with forward intensity-modulated radiotherapy significantly spared the heart and left anterior descending artery compared to generated free-breathing plans based on mean doses - free-breathing vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy, P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66 cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P = 0.007) - whereas they revealed no additional burden on the ipsilateral lung. Reproducible deep-inspiration breath-hold and free-breathing plans with inverse intensity-modulated radiotherapy provided similar organ at risk sparing by reducing the mean doses to the left ventricle, left anterior descending artery, heart, V10-V20 of the heart and right ventricle. However, forward intensity-modulated radiotherapy showed significant reduction in doses to the left ventricle, left anterior descending artery, heart, right ventricle, and contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses for free-breathing vs reproducible deep-inspiration breath-hold of the proximal left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50 Gy isodose line of the proximal left anterior descending artery were 6.6 vs 3.3 cm and of the distal left anterior descending artery were 7.4 vs 4.1 cm, with forward intensity-modulated radiotherapy. Overall reduction in mean doses to proximal and distal left anterior descending artery with deep-inspiration breath-hold irradiation was 39% (P = 0.02) and 52% (P = 0.002), respectively.nnnCONCLUSIONSnWe found a significant reduction of radiation exposure to the contralateral breast, left and right ventricles, as well as of proximal and especially distal left anterior descending artery with the deep-inspiration breath-hold technique with forward intensity-modulated radiotherapy planning.

Preoperative treatment planning with intraoperative optimization can achieve consistent high-quality implants in prostate brachytherapy.

Advances in brachytherapy treatment planning systems have allowed the opportunity for brachytherapy to be planned intraoperatively as well as preoperatively. The relative advantages and disadvantages of each approach have been the subject of extensive debate, and some contend that the intraoperative approach is vital to the delivery of optimal therapy. The purpose of this study was to determine whether high-quality permanent prostate implants can be achieved consistently using a preoperative planning approach that allows for, but does not necessitate, intraoperative optimization. To achieve this purpose, we reviewed the records of 100 men with intermediate-risk prostate cancer who had been prospectively treated with brachytherapy monotherapy between 2006 and 2009 at our institution. All patients were treated with iodine-125 stranded seeds; the planned target dose was 145 Gy. Only 8 patients required adjustments to the plan on the basis of intraoperative findings. Consistency and quality were assessed by calculating the correlation coefficient between the planned and implanted amounts of radioactivity and by examining the mean values of the dosimetric parameters obtained on preoperative and 30 days postoperative treatment planning. The amount of radioactivity implanted was essentially identical to that planned (mean planned radioactivity, 41.27 U vs. mean delivered radioactivity, 41.36 U; R(2) = 0.99). The mean planned and day 30 prostate V100 values were 99.9% and 98.6%, respectively. The mean planned and day 30 prostate D90 values were 186.3 and 185.1 Gy, respectively. Consistent, high-quality prostate brachytherapy treatment plans can be achieved using a preoperative planning approach, mostly without the need for intraoperative optimization. Good quality assurance measures during simulation, treatment planning, implantation, and postimplant evaluation are paramount for achieving a high level of quality and consistency.

Select men benefit from androgen deprivation therapy delivered with salvage radiation therapy after prostatectomy

Background:Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy.Methods:We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan–Meier and log-rank tests compared FFS with and without ADT.Results:Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8–18.1) ADT). Median SRT dose was 70u2009Gy (IQR 70–70), and median follow-up after SRT was 6.7 years (IQR 4.5–10.8). On Coxs proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42–0.86; P=0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ⩾0.5u2009ngu2009ml−1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P=0.003), but not for men with favorable disease (81.2% vs 78.0%; P=0.971).Conclusions:The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ⩾0.5u2009ngu2009ml−1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA <0.5u2009ngu2009ml−1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesis-generating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.

Use of fluorodeoxyglucose positron emission tomography for diagnosis of bleomycin-induced pneumonitis in Hodgkin lymphoma

Abstract Bleomycin is an antineoplastic agent causing fatal pulmonary toxicity. Early diagnosis of bleomycin-induced pneumonitis is crucial to prevent irreversible damage. Pulmonary function tests are unreliable for identifying risk of bleomycin toxicity. Fluorodeoxyglucose PET/CT scanning can reveal inflammation secondary to pneumonitis but is not sufficiently specific for diagnosis. We retrospectively analyzed scans from 77 patients with Hodgkin lymphoma (median age 41 years, mean bleomycin dose 134u2009mg) to evaluate bleomycin-induced pneumonitis. We identified 13 patients with abnormal lung uptake of fluorodeoxyglucose. Tracer activity was predominantly diffuse, bilateral, in the lower lobes and subpleural areas. Interim scanning during treatment revealed pneumonitis in eight of 13 patients (asymptomatic in six). One asymptomatic patient died of bleomycin toxicity. For remaining 12 patients, bleomycin was discontinued and methylprednisolone given, all showed resolution of the pneumonitis. These findings suggest that routine interim or end-of-treatment FDG-PET/CT scanning could be beneficial for alerting clinicians to asymptomatic bleomycin-induced toxicity.

Prostate Cancer Risk Grouping and Selection Criteria Based on Radiation Oncology Perspective

Since many decades, TNM staging has been widely used for almost all the cancer-diagnosed cases, to ensure the common language among the literature and medicine, but specifically to prostate cancer, treatment decisions have been more driven by diagnostic findings such as pretreatment PSA, age, biopsy-based Gleason score, and treatment options as well as the TNM staging. The management of prostate cancer includes a variety of approaches starting from active surveillance for very early stage. Intermediate stages could be treated with either surgery, radiotherapy, or brachytherapy with definitive intent. More locally advanced stages need combination of hormonal treatment with radiotherapy and/or surgery. Following the several published surgical nomograms to differentiate the patients more suitable for surgery, various attempts to provide probability graphs, nomograms, lookup tables, and neural networks were published and also validated by various groups in order to clarify the heterogeneity among groups and to distinguish patient selections between surgery, external beam therapy, brachytherapy, and hormonal therapy. Among the published, more than 20 nomograms, NCCN, TNM, and D’Amico groupings are the well-known and mostly used evaluation systems. The traditional three-group and new five-group risk stratifications and the new prostate grade grouping 1–5 will be in use to predict the risk of PSA recurrence following surgery and radiotherapy. The aim of this chapter is to provide a scope on these nomograms and comparison to each other in clinical practice.

Modern Radiotherapy Era in Breast Cancer

Radiation therapy (RT) is one of the major treatment modalities that are used in breast cancer treatment, and depending on the chest-wall anatomy, RT fields have to be customized. Techniques used in planning have been evolving since last two decades from two dimensional (2D) to three-dimensional (3D), while intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and even proton therapy have been an option in daily approach. In addition, technological hardware and software advances in delivery and planning systems, total treatment duration of breast RT have been shortened in last decades along with recent hypofractionated radiotherapy schemes or emerging partial-breast irradiation protocols. The other attractive approach—accelerated partial breast irradiation (APBI) could be a reasonable option for highly selected subpopulation of early-stage breast cancer patients out of a clinical trial. Long-term follow-up results have emerged heart and coronary sparing with maximum safety and efficacy. The most important advance could be named as cardiac sparing—deep breathhold approach—in all the modern technique improvement. Although most advanced techniques in management of breast cancer have not been verified to increase survival, we suggest recommending resource stratified advanced in order to provide best technical and clinical care in this long-term survivor candidates.

Adjuvant or Salvage Radiotherapy in Postoperative Prostate Cancer

Prostate-specific antigen (PSA) screening increased the diagnosis of prostate cancer at a localized stage to be treated with a curative intent; approximately half of them undergo radical prostatectomy, and roughly one third of surgically treated patients are expected to experience a recurrence in 10 years’ follow-up. Once PSA failure occurs, many develop distant metastases at a median of 8 years and afterward followed by cancer-related death at a median of 5 years. Biochemical failure risk after radical prostatectomy is mainly expected mostly in men with any of the following features: detectable postoperative PSA, positive surgical margins, extraprostatic extension of tumor (T3a), seminal vesicle invasion (T3b), and Gleason score ≥ 8. The radiotherapy in the undetectable PSA environment (<0.01 ng/mL) within 4 months after prostatectomy is termed as “adjuvant, ” while radiotherapy in rising PSA within any time after prostatectomy is defined as “salvage. ”

Modern Radiotherapy Techniques in Lung Cancer

During the last decade, technology has provided remarkable improvements and accessibility to cutting edge techniques in many departments. The major goal is set to improve quality of life and toxicity profiles of mediastinal treatments without compromising the local control and overall survival. Moving from 2D to 3D and 4D simulation has exposed the secrets of moving targets to individualize margins on specified targets and organs at risk, in addition to ensure precision to minimize the interobserver variability in target delineation via incorporation of FDG–PET fusion in customization. Image-guided radiotherapy with either planar or volumetric imaging increased accurate and appropriate daily localization, promoting comfort to encourage dose escalation or respiratory phase-specific treatment strategies along with motion management in thoracic malignancies. As randomized trials are lacking for many new technologies, knowledge-based tailoring and implementation of any site and stage-specific requirement per patient has been a common practice in the recent years, such as SBRT, IMRT, VMAT, or protons.

Selection Criteria for Definitive Treatment Approach in Thoracic Malignancies: Radiation Oncology Perspective

Although surgical resection is directly related with anatomic boundaries and as a summary an all-or-none modality, even surgical prognosticators to define post-resection functional status could remain suboptimal. Radiotherapy, on the other site, is not an anatomical dissection, not a straightforward modality, and cannot be easily defined in numbers because of lack of correlation of effected anatomic units and heterogeneity of the effect on each unit. So evaluation before radiotherapy is overall a risk assessment with the baseline functional status and radiotherapy-induced expected loss in the function. Radiotherapy-triggered changes are gradual over time, sometimes as unusual reactions or hypersensitivity pneumonitis, and the compensation by the unirradiated lung is unpredictable. Overall, a radiation oncologist is expected to minimize the potential toxicity risks in an environment of various combinations of medical inoperability, poor pulmonary functionality, riskily localized or large parenchyma endangering bulky tumors, etc. and is mostly asked to be prepared to accept potential morbidities in this referred population with great expectations who will face a certain death if not treated.