Comparison of acute toxicities between contemporary forward‐planned 3D conformal radiotherapy and inverse‐planned intensity‐modulated radiotherapy for whole breast radiation

The use of inverse‐planned intensity‐modulated radiation therapy for whole breast radiation treatment has become more prevalent, but this may impose an increased cost on the health system. We hypothesized that when applied with the same treatment planning goals, tangential forward‐planned field‐in‐field 3D conformal radiotherapy and tangential inverse‐planned intensity‐modulated radiotherapy would be associated with comparable toxicities. Women who underwent tangential whole breast irradiation at our institution from 2011 to 2015 planned using either forward‐planned field‐in‐field 3D conformal radiotherapy or intensity‐modulated radiotherapy were retrospectively analyzed. Grade 2+ Radiation dermatitis was the primary endpoint. A total of 201 and 212 women had undergone field‐in‐field 3D conformal radiotherapy and intensity‐modulated radiotherapy, respectively. No differences were observed between the two modalities regarding acute radiation dermatitis, breast pain, or fatigue. In a multivariable logistic regression that incorporated the use of boost, hypofractionation, use of chemotherapy, patient positioning, use of a supraclavicular field, and breast planning target volume, intensity‐modulated radiotherapy was not correlated with different rates of Grade 2+ radiation dermatitis. This study supports the routine first‐line use of field‐in‐field 3D conformal radiotherapy for whole breast radiation instead of tangential intensity‐modulated radiotherapy from the standpoint of equivalence in acute toxicity. Further investigation is needed to assess whether there are subgroups of women who may still benefit from intensity‐modulated radiotherapy.     

Outcomes with intraoperative radiation therapy for early‐stage breast cancer

Adjuvant radiation therapy has been associated with improved local control following breast‐conserving surgery. Traditionally, treatment has been delivered with whole breast irradiation over 3‐6 weeks or partial breast irradiation over 1‐3 weeks. However, intraoperative radiation therapy (IORT) has emerged as a technique that delivers a single dose of radiotherapy at the time of surgery for early‐stage breast cancers. We report initial outcomes and acute toxicities with intraoperative radiation from a single institution. Patients with DCIS or Stage I‐II breast cancer who underwent lumpectomy and sentinel lymph node biopsy (nodal sampling excluded in some cases) were included. All patients in this analysis were treated with IORT as at the time of surgery, 20 Gy in 1 fraction with 50 kV x‐ray. Patients were treated at a single institution between 2011 and 2019. Follow‐up was per standard institutional protocol. Two hundred and one patients were included in the analysis, with a median follow‐up of 23 months (range: 0‐73 months). Median age was 71 years old. Overall, 4 (2.0%) patients had DCIS, 186 (92.5%) patients had Stage 1 disease, and 11 patients had (5.5%) Stage 2 disease. All patients were estrogen receptor‐positive, 175 (87.9%) progesterone receptor‐positive, and 1 (0.5%) HER2 amplified. The crude rate of local recurrence was 2.0% (n = 4) and distant metastasis rate was 0.5% (n = 1). The rate of arm lymphedema was 0.5% (n = 1) and chronic telangiectasia rate was 1.1% (n = 2). Intraoperative radiation therapy, in a cohort of low‐risk patients, demonstrated low rates of recurrence and reproducibility in a multi‐disciplinary setting. Further follow‐up, analysis of patient satisfaction and cosmesis, and comparison to whole breast irradiation and partial breast techniques is necessary in order to further validate these findings.     

Acute toxicities after proton beam therapy following breast‐conserving surgery for breast cancer: Multi‐institutional prospective PCG registry analysis

We investigated adverse events (AEs) and clinical outcomes for proton beam therapy (PBT) after breast‐conserving surgery (BCS) for breast cancer. From 2012 to 2016, 82 patients received PBT in the prospective multi‐institutional Proton Collaborative Group registry. AEs were recorded prospectively at each institution. Median follow‐up was 8.1 months. Median dose was 50.4 Gy in 28 fractions. Most patients received a lumpectomy bed boost (90%) and regional nodal irradiation (RNI)(83%). Six patients (7.3%) experienced grade 3 AEs (5 with dermatitis, 5 with breast pain). Body mass index (BMI) was associated with grade 3 dermatitis (P = .015). Fifty‐eight patients (70.7%) experienced grade ≥2 dermatitis. PBT including RNI after BCS is well‐tolerated. Elevated BMI is associated with grade 3 dermatitis.     

Effect of radiation therapy and Photofrin® on tissue response in a rat model

Treatment of advanced carcinomas of the head and neck may benefit from adjuvant photodynamic therapy and brachyradiotherapy. To date, however, there has been no controlled study to evaluate whether high-dose irradiation can be safely accomplished without major tissue reaction in the presence of high circulating doses of Photofrin, the photosensitizing agent used in photodynamic therapy. Thirty adult male white rats were involved in the study. Fifteen rats received Photofrin 5 mg/kg intravenously, and 15 rats received the same volume of sterile saline intravenously. At 48 hours following injection, each rat received 1,000 cGy of radiation to a 3 × 5 cm area of dorsal skin using a cobalt linear accelerator unit. Skin changes postradiation were observed for degree of erythema, blistering, necrosis, and sloughing. Five rats from the Photofrin and control radiation groups were sacrificed on days 2, 7, and 21 postradiotherapy. Skin changes in each animal were identical with mild erythema lasting from 10–14 days postradiotherapy. There was no evidence of blistering, necrosis, or sloughing of skin in any of the animals studied. Histologic evaluation of the irradiated skin after sacrifice demonstrated no difference between the Photofrin and saline-irradiated groups. As well, the histologic recovery from acute radiation injury was also identical. This controlled study demonstrates that radiation therapy may be safely administered without increased morbidity when tissue concentrations necessary to perform photodynamic therapy are present. © 1993 Wiley-Liss, Inc.     

Post‐mastectomy Radiotherapy for pT3N0 Breast Cancers: A Retrospective,Multi‐Institution Review

The role of post‐mastectomy radiotherapy for pT3N0 breast cancers remains undefined. The purpose of this study was to report institutional outcomes for women with pT3N0 breast cancers treated with and without post‐mastectomy radiotherapy. We collected data from two large tumor registries on pT3N0 breast cancers diagnosed between 1985 and 2014. Kaplan–Meier estimates were used to analyze freedom from local‐regional recurrence (FFLR), relapse free survival, and overall survival. This analysis identified 93 women with pT3N0 breast cancers. Of these, 53 received post‐mastectomy radiotherapy and 40 did not. Median follow‐up was 6.2 years and 5.3 years in the non‐post‐mastectomy radiotherapy and post‐mastectomy radiotherapy cohorts, respectively. Women not undergoing post‐mastectomy radiotherapy were more likely to be diagnosed in the 1980s and 1990s and were less likely to receive systemic therapies than women receiving post‐mastectomy radiotherapy (p < 0.05). There was a trend toward increased FFLR in the women receiving post‐mastectomy radiotherapy (p = 0.15). FFLR in the post‐mastectomy radiotherapy cohort was 98% at both 5 and 10 years. For women not receiving post‐mastectomy radiotherapy, FFLR was 88% at both 5 and 10 years. Women not receiving post‐mastectomy radiotherapy in our study had an isolated local‐regional failure rate of 12% at 10 years, despite receiving inferior systemic treatment by current standards. Local‐regional control after post‐mastectomy radiotherapy for pT3N0 breast cancers was excellent. Further research is needed to define post‐mastectomy radiotherapy indications for this patient population when receiving chemotherapy and endocrine therapy in line with current guidelines.     

Intraoperative High-Dose-Rate Brachytherapy—A Novel Technique in the Surgical Management of Axillary Recurrence

Abstract:  Treating recurrent disease in the axilla is a challenging and complex clinical problem. Several reports in the literature suggest better outcomes with the combination of both surgery and radiation therapy than either modality alone. However, the available options for re-treatment are limited by the extent of disease at relapse, and the prior therapy that the patient has already received. The choice of re-irradiation using conventional external beam therapy is generally limited because of the risk of exceeding the radiation tolerance of the brachial plexus. In lieu of our concerns regarding excessive morbidity from re-irradiation with external radiation therapy when treating an axillary relapse, we applied intraoperative high-dose-rate brachytherapy (HDR-IORT) at the time of surgical resection ± a modest dose of postoperative external beam radiation therapy. In this paper, we describe the feasibility of HDR-IORT technique in three patients presenting with recurrent disease in the axilla.     

Modern radiotherapy for modern surgeons: an update on radiation oncology

Changes in the practice of radiation oncology have been significant over the last decade and continue to develop at an exciting rate. These advances range from our understanding of the increasingly important role of radiotherapy in the adjuvant and definitive settings to huge technological progress in the areas of tumour delineation, treatment planning, delivery and verification. In many cases, benefits have resulted from the ability of modern radiotherapy to deliver high doses with great accuracy and increasing safety in a highly individualized manner. This has impacted favourably on the management of all major malignancies as discussed in this paper. A good understanding of what can be achieved with modern radiotherapy has never been more important in ensuring an effective multidisciplinary approach to cancer management.     

Association of age and response to androgen‐deprivation therapy with or without radiotherapy for prostate cancer: data from CaPSURE

Study Type – Therapy (prospective cohort)
Level of Evidence 2b

OBJECTIVE

To assess whether the response to primary androgen‐deprivation therapy (PADT) and radiotherapy (RT) plus adjuvant ADT would be muted in older men, as their tumours might already be relatively androgen insensitive, because serum testosterone levels decline with increasing age.

PATIENTS AND METHODS

Using the Cancer of the Prostate Strategic Urologic Research Endeavor database, we conducted an observational study evaluating two groups of men treated for prostate cancer from 1995 to 2006. One group of 1748 men was treated with PADT and the second group of 612 men was treated with RT (external beam RT or brachytherapy) with neoadjuvant and/or adjuvant ADT. We tested whether age was a predictor of disease progression in the PADT group and prostate‐specific antigen (PSA) recurrence in the RT + ADT group (Phoenix definition). Secondary outcomes were all cause (ACM) and prostate cancer‐specific mortality (PCSM).

RESULTS

In both univariate and multivariate analysis stratifying by clinical risk group, age (<65, 65–69, 70–74, and ≥75 years) was not associated with the risk of secondary treatment or PSA recurrence for the PADT and the RT + ADT groups, respectively. Age category had no relationship to increased ACM or PCSM for the RT + ADT group. However, for the PADT group the oldest category (>75 years) had an increased hazard ratio (2.26, 95% confidence interval 1.04–4.88; P = 0.02) for ACM, but a decreased ratio for PCSM (0.29, 0.21–0.42; P < 0.01).

CONCLUSION

If we assume that age is a valid proxy measure for free available testosterone levels, then these levels do not seem to affect the likelihood of response to ADT, either used alone or combined with RT.     

Radiation therapy and photodynamic therapy for biliary tract and ampullary carcinomas

The purpose of radiation therapy for unresectable biliary tract cancer is to prolong survival or prolong stent patency, and to provide palliation of pain. For unresectable bile duct cancer, there are a number of studies showing that radiation therapy is superior to the best supportive care. Although radiation therapy is used in many institutions, no large randomized controlled trials (RCTs) have been performed to date and the evidence level supporting the superiority of this treatment is low. Because long-term relief of jaundice is difficult without using biliary stenting, a combination of radiation therapy and stent placement is commonly used. As radiation therapy, external-beam radiation therapy is usually performed, but combined use of intraluminal brachytherapy with external beam radiation therapy is more useful for making the treatment more effective. There are many reports demonstrating improved response rates as well as extended survival and time to recurrence achieved by this combination therapy. Despite the low level of the evidence, this combination therapy is performed at many institutions. It is expected that multiinstitutional RCTs will be carried out. Unresectable gallbladder cancer with a large focus is usually extensive, and normal organs with high radio sensitivity exist contiguously with it. Therefore, only limited anticancer effects are to be expected from external beam radiation therapy for this type of cancer. The number of reports on ampullary cancer is small and the role of radiation therapy in this cancer has not been established. Combination treatment for ampullary cancer consists of either a single use of intraoperative radiation therapy, postoperative external beam radiation therapy or intraluminal brachytherapy, or a combination of two or three of these therapies. Intraoperative radiation therapy is superior in that it enables precise irradiation to the target site, thereby protecting adjacent highly radiosensitive normal tissues from irradiation. There are reports showing extended survival, although not significant, in groups undergoing intraoperative or postoperative radiation therapy compared with groups without radiation therapy. To date, there are no reports of large RCTs focusing on the significance of radiation therapy as a postoperative adjuvant treatment, so its usefulness as a postoperative adjuvant treatment is not proven. An alternative treatment is photodynamic therapy. There is an RCT demonstrating that, in unresectable bile duct cancer, extended survival and improved quality of life (QOL) have been achieved through a combination of photodynamic therapy and biliary stenting, compared with biliary stenting alone. Results from large RCTs are desired.     

Intraoperative irradiation: a new technique in pediatric oncology

Adverse effects on normal tissue are the principal limiting factor in the use of radiation therapy. Maturing tissues are most susceptible to these side effects, so high-dose applications can be a particularly difficult challenge in children. Intraoperative radiation therapy (IORT) enables the radiation oncologist to displace or shield dose-limiting organs or structures. These first two cases of children treated with IORT suggest that IORT, used alone or in conjunction with external beam irradiation, may be useful in the pediatric age group.     

Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes

Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x‐rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long‐term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.     

Carbon‐ion radiation therapy for prostate cancer

In 1994, carbon‐ion radiotherapy was started at the National Institute of Radiological Sciences using the Heavy‐Ion Medical Accelerator in Chiba. Between June 1995 and March 2000, two phase I/II dose escalation studies (protocols 9402 and 9703) of hypofractionated carbon‐ion radiotherapy for both early‐ and advance‐stage prostate cancer patients had been carried out to establish radiotherapy technique and to determine the optimal radiation dose. To validate the feasibility and efficacy of hypofractionated carbon‐ion radiotherapy, a phase II study (9904) was initiated in April 2000 using the shrinking field technique and the recommended dose fractionation (66 gray equivalents in 20 fractions over 5 weeks) obtained from the phase I/II studies, and was successfully completed in October 2003. The data from 175 patients in the phase II study showed the importance of an appropriate use of androgen deprivation therapy according to tumor risk group. Since November 2003, carbon‐ion radiotherapy for prostate cancer was approved as “Highly Advanced Medical Technology” from the Ministry of Health, Labor, and Welfare, and since then approximately 1100 patients have received carbon‐ion radiotherapy as of July 2011. In this review, we introduce our steps thorough three clinical trials carried out at National Institute of Radiological Sciences, and show the updated data of carbon‐ion radiotherapy obtained from approximately 1000 prostate cancer patients. In addition, our recent challenge and future direction will be also described.     

简单调强技术在胃癌术后放疗中的应用研究

目的研究简单调强放射治疗（sIMRT）技术在胃癌术后放射治疗中的剂量学特点,为临床提供参考。方法选取2012年2—6月间在南京医科大学附属淮安第一医院接受治疗的12例胃癌术后患者,分别设计三维适形放疗（3D-CRT）、5野调强放射治疗（IMRT）计划和5野简单调强放射治疗（sIMRT）计划,其中3D．CRT采用上下分野照射,调强放疗均选取20°、80°、180°、280°和34005个照射野。应用剂量体积直方图（DVH）比较3种计划的适形度指数、不均匀性指数、正常组织受照剂量特点、机器治疗总跳数及治疗总时间。结果sIMRT和IMRT计划适形度优于3D—CRT计划,但不均匀性亦甚于3D．CRT计划,差异有统计学意义（均P〈0．05）。在不同的放疗剂量下,sIMRT计划受照射的肝脏和双肾体积百分比均低于3D．CRT计划（均P〈0．05）,与IMRT计划相近（均P〉0．05）。sIMRT计划的机器总跳数和总治疗时间均少于IMRT计划和3D—CRT计划。结论sIMRT技术和IMRT技术用于胃癌术后放疗,其剂量分布明显优于3D—CRT技术;但sIMRT技术治疗时间最短,在临床应用具有更便捷的优势。