The impact of dose escalation on secondary cancer risk after radiotherapy of prostate cancer

PURPOSE: To estimate secondary cancer risk due to dose escalation in patients treated for prostatic carcinoma with three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated RT (IMRT), and spot-scanned proton RT. METHODS AND MATERIALS: The organ equivalent dose (OED) concept with a linear-exponential, a plateau, and a linear dose-response curve was applied to dose distributions of 23 patients who received RT of prostate cancer. Conformal RT was used in 7 patients, 8 patients received IMRT with 6- and 15-MV photons, and 8 patients were treated with spot-scanned protons. We applied target doses ranging from 70 Gy to 100 Gy. Cancer risk was estimated as a function of target dose and tumor control probability. RESULTS: At a 100-Gy target dose the secondary cancer risk relative to the 3D treatment plan at 70 Gy was +18.4% (15.0% for a plateau model, 22.3% for a linear model) for the 6-MV IMRT plan, +25.3% (17.0%, 14.1%) for the 15-MV IMRT plan, and -40.7% (-41.3%, -40.0%) for the spot-scanned protons. The increasing risk of developing a radiation-associated malignancy after RT with increasing dose was balanced by the enhanced cure rates at a larger dose. CONCLUSIONS: Cancer risk after dose escalation for prostate RT is expected to be equal to or lower than for conventional 3D treatment at 70 Gy, independent of treatment modality or dose-response model. Spot-scanned protons are the treatment of choice for dose escalation because this therapy can halve the risk of secondary cancers.     

Optimized dose coverage of regional lymph nodes in breast cancer: the role of intensity-modulated radiotherapy

PURPOSE: To determine whether the use of intensity-modulated radiotherapy (IMRT) would lead to improved dosimetry for the breast and regional nodes. METHODS AND MATERIALS: Ten patients with left-sided breast cancer were selected. The clinical target volume included left breast and internal mammillary (IM), supraclavicular (SC), and axillary (AX) nodes. The critical structures included heart, right and left lungs, contralateral breast, esophagus, thyroid, and humeral head. Conventional and a series of IMRT plans were generated for comparison. RESULTS: The average heart D(3) was reduced from 31.4 +/- 18.9 with three-dimensional conformal radiotherapy (3D-CRT) to 15 +/- 7.2 Gy with 9-field (9-FLD IMRT). The average left lung D(30) was also decreased from 27.9 +/- 11.5 Gy (3D-CRT) to 12.6 +/- 8.2 Gy (9-FLD IMRT). The average contralateral breast D(2) was reduced from 4.4 +/- 5.3 Gy (3D-CRT) to 1.8 +/- 1.2 Gy (4-FLD IMRT). Esophagus D(2) was increased from 9.3 +/- 8.1 Gy (3D-CRT) to 29.4 +/- 5.4 (9-FLD IMRT); thyroid D(50) was increased from 0.9 +/- 0.6 Gy (3D-CRT) to 11.9 +/- 6.6 (9-FLD IMRT); humeral head D(2) was increased from 36.1 +/- 13.1 Gy (3D-CRT) to 39.9 +/- 6.5 (9-FLD IMRT). CONCLUSIONS: The use of IMRT improves breast and regional node coverage while decreasing doses to the lungs, heart, and contralateral breast when compared with 3D-CRT. Doses to esophagus, thyroid, and humeral head, however, were increased with IMRT.     

Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy

PURPOSE: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade > or = 3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. RESULTS: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade > or = 3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). CONCLUSIONS: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade > or = 3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.     

Long-term outcome following three-dimensional conformal/intensity-modulated external-beam radiotherapy for clinical stage T3 prostate cancer

OBJECTIVE: To report the long-term tumor control and survival outcomes after conformal external-beam radiotherapy for patients with clinical stage T3 prostate cancer. METHODS: Between 1988 and 2000, 296 patients with clinical stage T3 prostate cancer were treated with three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Of these, 130 patients (44%) had stage T3a (extracapsular extension without seminal vesicle involvement [SVI]) and 166 patients (56%) had stage T3b disease (SVI). Prior to radiotherapy, 189 patients (43%) were treated with short-course androgen-deprivation therapy (ADT). The median follow-up time was 8 yr. RESULTS: The 5- and 10-yr prostate-specific antigen (PSA) relapse-free survival (PRFS) outcomes for stage T3a tumors were 69% and 44%, respectively. The corresponding PRFS outcomes for T3b tumors were 49% and 32% (p=0.005). Despite the presence of locally advanced disease, the 5- and 10-yr local progression-free survival (LPFS) outcomes for all patients were 87% and 83%. Among patients who received > or =8100 cGy and ADT, the 5- and 10-yr local control rates were 96% and 88%. The 5- and 10-yr distant metastases-free survival (DMFS) outcomes for stage T3a tumors were 85% and 73%. The corresponding DMFS outcomes for T3b tumors were 49% and 32% (p=0.005). Multivariate analysis demonstrated that ADT conferred a 7-fold risk reduction for local failure. Pretreatment PSA levels and the presence of SVI on clinical staging were important predictors of distant metastases. CONCLUSIONS: Conformal radiotherapy for T3 prostate cancer is associated with excellent tumor control and survival outcomes. These results are at least comparable to reported outcomes from surgical series for T3 disease and substantiate the role of radiotherapy as the standard management option for locally advanced stage prostate cancer.     

32例妇科恶性肿瘤术后调强适形放射治疗分析

目的 探讨调强适形放射治疗（IMRT）在妇科恶性肿瘤患者术后治疗中的效果及价值。方法 32例子宫颈癌、子宫内膜癌术后患者（KPS≥70）在放疗前均行1～3个周期的化疗,而后给予全程IMRT。其中17例为术后、化疗后预防性照射,15例为术后、放疗和（或）化疗后腹膜后淋巴结转移和（或）盆腔壁复发的放疗。结果 32例患者均完成全程放射治疗,预防性照射的计划靶区（PTV）中位剂量为56．8Gy;腹膜后淋巴结转移、盆壁复发的胛V中位剂量为60．6Gy,90％的等剂量曲线可以覆盖99％以上的肉眼肿瘤靶区（GTV）体积。小肠、膀胱、直肠、肾脏和脊髓的中位剂量分别为21．3Gy、37．8Gy、35．3Gy、8．5Gy和22．1Gy。14例患者出现Ⅰ～Ⅱ级消化道反应,其中Ⅱ级反应者3例,I级反应者11例;5例出现Ⅰ～Ⅱ度骨髓抑制;12例出现Ⅰ级皮肤反应。1年生存率为100％。预防性照射的2、3年生存率均为100％;腹膜后淋巴结转移和（或）盆腔壁复发患者的2、3年生存分别为5／7和3／6。结论 IMRT对妇科恶性肿瘤术后患者的预防性照射和复发患者的放疗均可获得理想的剂量分布,邻近危险器官得到保护,临床近期疗效满意。     

Patterns of Practice in Canadian Radiation Treatment Centres: Results of a National Survey

PurposeRadiation therapy has changed rapidly over the past decade due to the application of technological advances. A survey was conducted of radiation treatment centres in Canada to establish current patterns of practice across the country. Areas of inquiry included treatment techniques and image verification, as well as roles and responsibilities of radiation therapists (RTs).Methods and MaterialsIn January 2016, a survey was sent to managers of the 46 radiation treatment centres in Canada. This survey sought information on a range of staffing and practice variables for the fiscal year 2014/2015.ResultsOf the 46 centres contacted, 37 centres responded, representing an 80.4% response rate. Survey results showed that the use of volumetric arc therapy and intensity-modulated radiation therapy is common across Canada for several anatomic sites, as well as the use of daily pretreatment image verification. A high degree of variability exists for imaging modality (two dimensional vs. three dimensional) for some sites, including brain, head and neck, and lung. RTs' responsibilities have expanded uniformly across the country, with RTs involved in organ-at-risk contouring and on-treatment image approval at the majority of centres. Despite this role expansion, specialty roles in areas of quality and applications expertise are still rare.ConclusionsRadiation therapy in Canada has transitioned to high-technology treatment techniques with relative consistency across the country. There is, however, variation in the imaging modality used for daily verification. Canada may benefit from consensus guidelines on the application of three-dimensional imaging for treatment verification. While RTs have expanded their responsibilities, role definition for RTs working in supervisory or supporting positions has not kept pace at many centres and it is unclear if RTs are supported in their expanded accountabilities.     

Dosimetric Comparison Between 2-Dimensional Radiation Therapy and Intensity Modulated Radiation Therapy in Treatment of Advanced T-Stage Nasopharyngeal Carcinoma: To Treat Less or More in the Planning Organ-At-Risk Volume of the Brainstem and Spinal Cord

The aim of this study is to evaluate the deficiencies in target coverage and organ protection of 2-dimensional radiation therapy (2DRT) in the treatment of advanced T-stage (T3-4) nasopharyngeal carcinoma (NPC), and assess the extent of improvement that could be achieved with intensity modulated radiation therapy (IMRT), with special reference to of the dose to the planning organ-at-risk volume (PRV) of the brainstem and spinal cord. A dosimetric study was performed on 10 patients with advanced T-stage (T3-4 and N0-2) NPC. Computer tomography (CT) images of 2.5-mm slice thickness of the head and neck were acquired with the patient immobilized in semi-extended-head position. A 2D plan based on Ho’s technique, and an IMRT plan based on a 7-coplanar portals arrangement, were established for each patient. 2DRT was planned with the field borders and shielding drawn on the simulator radiograph with reference to bony landmarks, digitized, and entered into a planning computer for reconstruction of the 3D dose distribution. The 2DRT and IMRT treatment plans were evaluated and compared with respect to the dose-volume histograms (DVHs) of the targets and the organs-at-risk (OARs), tumor control probability (TCP), and normal tissue complication probabilities (NTCPs). With IMRT, the dose coverage of the target was superior to that of 2DRT. The mean minimum dose of the GTV and PTV were increased from 33.7 Gy (2DRT) to 62.6 Gy (IMRT), and 11.9 Gy (2DRT) to 47.8 Gy (IMRT), respectively. The D₉₅ of the GTV and PTV were also increased from 57.1 Gy (2DRT) to 67 Gy (IMRT), and 45 Gy (2DRT) to 63.6 Gy (IMRT), respectively. The TCP was substantially increased to 78.5% in IMRT. Better protection of the critical normal organs was also achieved with IMRT. The mean maximum dose delivered to the brainstem and spinal cord were reduced significantly from 61.8 Gy (2DRT) to 52.8 Gy (IMRT) and 56 Gy (2DRT) to 43.6 Gy (IMRT), respectively, which were within the conventional dose limits of 54 Gy for brainstem and of 45 Gy for spinal cord. The mean maximum doses deposited on the PRV of the brainstem and spinal cord were 60.7 Gy and 51.6 Gy respectively, which were above the conventional dose limits. For the chiasm, the mean dose maximum and the dose to 5% of its volume were reduced from 64.3 Gy (2DRT) to 53.7 Gy (IMRT) and from 62.8 Gy (2DRT) to 48.7 Gy (IMRT), respectively, and the corresponding NTCP was reduced from 18.4% to 2.1%. For the temporal lobes, the mean dose to 10% of its volume (about 4.6 cc) was reduced from 63.8 Gy (2DRT) to 55.4 Gy (IMRT) and the NTCP was decreased from 11.7% to 3.4%. The therapeutic ratio for T3-4 NPC tumors can be significantly improved with IMRT treatment technique due to improvement both in target coverage and the sparing of the critical normal organ. Although the maximum doses delivered to the brainstem and spinal cord in IMRT can be kept at or below their conventional dose limits, the maximum doses deposited on the PRV often exceed these limits due to the close proximity between the target and OARs. In other words, ideal dosimetric considerations cannot be fulfilled in IMRT planning for T3-4 NPC tumors. A compromise of the maximal dose limit to the PRV of the brainstem and spinal cord would need be accepted if dose coverage to the targets is not to be unacceptably compromised. Dosimetric comparison with 2DRT plans show that these dose limits to PRV were also frequently exceeded in 2DRT plans for locally advanced NPC. A dedicated retrospective study on the incidence of clinical injury to neurological organs in a large series of patients with T3-4 NPC treated by 2DRT may provide useful reference data in exploring how far the PRV dose constraints may be relaxed, to maximize the target coverage without compromising the normal organ function.     

Forward-planned, multiple-segment, tangential fields with concomitant boost in the treatment of breast cancer

We report on the utility of forward-planned, 3-dimensional (3D), multiple-segment tangential fields for radiation treatment of patients with breast cancer. The technique accurately targets breast tissue and the tumor bed and reduces dose inhomogeneity in the target. By decreasing excess dose to the skin and lung, a concomitant boost to the tumor bed can be delivered during the initial treatment, thereby decreasing the overall treatment time by one week. More than 120 breast cancer patients have been treated with this breast conservation technique in our clinic. For each patient, a 3D treatment plan based upon breast and tumor bed volumes delineated on computed tomography (CT) was developed. Segmented tangent fields were iteratively created to reduce “hot spots” produced by traditional tangents. The tumor bed received a concomitant boost with additional conformal photon beams. The final tumor bed boost was delivered either with conformal photon beams or conventional electron beams. All patients received 45 Gy to the breast target, plus an additional 5 Gy to the surgical excision site, bringing the total dose to 50 Gy to the boost target volume in 25 fractions. The final boost to the excision site brought the total target dose to 60 Gy. With minimum follow-up of 4 months and median follow-up of 11 months, all patients have excellent cosmetic results. There has been minimal breast edema and minimal skin changes. There have been no local relapses to date. Forward planning of multi-segment fields is facilitated with 3D planning and multileaf collimation. The treatment technique offers improvement in target dose homogeneity and the ability to confidently concomitantly boost the excision site. The technique also offers the advantage for physics and therapy staff to develop familiarity with multiple segment fields, as a precursor to intensity-modulated radiation therapy (IMRT) techniques.