Pelvic Radiation and Normal Tissue Toxicity Nicholas, Sarah, MD; Chen, Linda, MD; Choflet, Amanda, DNP, RN ...
Seminars in radiation oncology,
10/2017, Letnik:
27, Številka:
4
Journal Article
Recenzirano
Radiation is a component of treatment for many pelvic malignancies, most often originating in the gynecologic, gastrointestinal, and genitourinary systems. Therefore, the management of acute and ...long-term side effects is an important part of practice as a radiation oncologist, and limiting morbidity is a primary goal. Toxicities vary and are dependent on treatment techniques. Advances in radiation delivery, imaging, and knowledge of underlying biologic determinants of radiation-induced normal tissue toxicity can guide treatment of acute and long-term side effects from pelvic radiation.
The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma.
An international committee ...of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours.
Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer.
These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations.
Abstract Objective To evaluate the effect of margin status and radiation dose in patients treated with radiation therapy (RT) for vulvar cancer. Clinical outcomes included vulvar recurrence (VR), ...relapse-free survival (RFS) and overall survival (OS). Methods We retrospectively reviewed the records of 300 patients with Stage I–IVA vulvar cancer treated between 1988 and 2009. Slides were reviewed and margin status was scored as negative (≥ 1 cm), close (< 1 cm) or positive after formalin fixation. Cox proportional hazards models were constructed to determine significant prognostic factors for vulvar relapse. Results Of 205 eligible patients, 69 (34%) had negative surgical margins, 116 (56%) had close margins and 20 (10%) had positive margins. Median follow-up time was 49 months. The 4-year RFS rate was 53% and OS was 73%. Of 78 recurrences, 62 had the vulva as the first site of recurrence. The 4-year rates of freedom from vulvar recurrence were 82%, 63% and 37% for those with negative, close and positive margins, respectively (p for trend = 0.005). On multivariate analysis, close margins (HR = 3.03, 95% CI 1.46–6.26) and positive margins (HR = 7.02, 95% CI 2.66–18.54) were associated with a significantly increased risk of vulvar relapse. Those who received a dose ≥ 56 Gy had a lower risk of relapse than those who received ≤ 50.4 Gy (p < 0.05). Though recurrences were noted with margins up to 9 mm, the highest risk of vulvar recurrence was associated with margins ≤ 5 mm (p = 0.002). Conclusions Close or positive margins were associated with a significantly increased risk of vulvar recurrence. Radiation with a dose ≥ 56 Gy may decrease the risk of vulvar recurrence.
The use of brachytherapy for the treatment of gynecologic malignancies, particularly cervical cancer, has a long and rich history that is nearly as long as the history of radiation oncology itself. ...From the first gynecologic brachytherapy treatments in the early 20th century to the modern era, significant transformation has occurred driven largely by advancements in technology. The development of high-dose rate sources, remote afterloaders, novel applicators, and 3-dimensional image guidance has led to improved local control, and thus improved survival, solidifying the role of brachytherapy as an integral component in the treatment of locally advanced cervical cancer. Current research efforts examining novel magnetic resonance imaging sequences, active magnetic resonance tracking, and the application of hydrogel aim to further improve local control and reduce treatment toxicity.
Abstract Purpose To evaluate clinical outcomes for women with recurrent endometrial cancer treated with 3D image-guided brachytherapy Methods and materials 44 women, of whom 13 had received prior RT, ...received salvage RT for vaginal recurrence from 9/03 to 8/11. HDR or LDR interstitial brachytherapy was performed under MR or CT guidance in 35 patients (80%); 9 (20%) had CT-guided HDR cylinder brachytherapy. The median cumulative dose in EQD2 was 75.5 Gy. Actuarial estimates of local failure (LF), disease-free (DFS) and overall survival (OS) were calculated by Kaplan–Meier. Results Histologic subtypes were endometrioid (EAC, 33), papillary serous/clear cell (UPSC/CC, 5) and carcinosarcoma (CS, 6). The 2-year DFS/OS rates were 75%/89% for EAC and 11%/24% for UPSC/CC/CS (both p < 0.01). On MVA, high tumor grade was associated with recurrence (HR 3.2 for grade 2, 9.6 for grade 3, p < 0.01). The LF rate at 2 years was 4% for patients without versus 39% for those with prior RT ( p = 0.1). Patients who had prior RT received lower cumulative doses at recurrence (66.5 Gy vs. 74.4 Gy, p < 0.01). The 2-year DFS/OS rates with and without prior RT were 26%/55% and 72%/80% (both p = 0.1). Four patients (9%) experienced grade 3 late toxicity, including 3 of 13 (23%) in the re-irradiation setting and 1 of 31 (3%) with no prior radiotherapy. Discussion 3D image-guided brachytherapy results in excellent local control for women with recurrent endometrial cancer, particularly with cumulative EQD2 doses greater than 70 Gy. Successful salvage of vaginal recurrence is related to tumor grade and histologic subtype.
FLASH Effects Induced by Orthovoltage X-Rays Miles, Devin; Sforza, Daniel; Wong, John W ...
International journal of radiation oncology, biology, physics,
11/2023, Letnik:
117, Številka:
4
Journal Article
Recenzirano
This work describes the first implementation and in vivo study of ultrahigh-dose-rate radiation (>37 Gy/s; FLASH) effects induced by kilovoltage (kV) x-ray from a rotating-anode x-ray source.
A ...high-capacity rotating-anode x-ray tube with an 80-kW generator was implemented for preclinical FLASH radiation research. A custom 3-dimensionally printed immobilization and positioning tool was developed for reproducible irradiation of a mouse hind limb. Calibrated Gafchromic (EBT3) film and thermoluminescent dosimeters (LiF:Mg,Ti) were used for in-phantom and in vivo dosimetry. Healthy FVB/N and FVBN/C57BL/6 outbred mice were irradiated on 1 hind leg to doses up to 43 Gy at FLASH (87 Gy/s) and conventional (CONV; <0.05 Gy/s) dose rates. The radiation doses were delivered using a single pulse with the widths up to 500 ms and 15 minutes at FLASH and CONV dose rates. Histologic assessment of radiation-induced skin damage was performed at 8 weeks posttreatment. Tumor growth suppression was assessed using a B16F10 flank tumor model in C57BL6J mice irradiated to 35 Gy at both FLASH and CONV dose rates.
FLASH-irradiated mice experienced milder radiation-induced skin injuries than CONV-irradiated mice, visible by 4 weeks posttreatment. At 8 weeks posttreatment, normal tissue injury was significantly reduced in FLASH-irradiated animals compared with CONV-irradiated animals for histologic endpoints including inflammation, ulceration, hyperplasia, and fibrosis. No difference in tumor growth response was observed between FLASH and CONV irradiations at 35 Gy. The normal tissue sparing effects of FLASH irradiations were observed only for high-severity endpoint of ulceration at 43 Gy, which suggests the dependency of biologic endpoints to FLASH radiation dose.
Rotating-anode x-ray sources can achieve FLASH dose rates in a single pulse with dosimetric properties suitable for small-animal experiments. We observed FLASH normal tissue sparing of radiation toxicities in mouse skin irradiated at 35 Gy with no sacrifice to tumor growth suppression. This study highlights an accessible new modality for laboratory study of the FLASH effect.
Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal ...models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, whereby radiotherapy of a tumor at one site can engender therapeutically significant responses in tumors at distant untreated sites. In this study, two subcutaneous cervical cancer tumors representing one primary and one metastatic tumor were generated in each animal. Only the primary tumor was treated and the responses of both tumors were monitored. The study was repeated as a function of different treatment parameters, including radiotherapy dose and dosing schedule of immunoadjuvant anti-CD40. The results consistently suggest that one fraction dose of radiotherapy with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses, with a significant increase in animal survival (
= 0.0004). Overall, 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow. Moreover, re-challenged responders to the treatment developed vitiligo, suggesting developed immune memory for this cancer. The findings offer a potential new therapy approach, which could be further investigated and developed for the treatment of advanced cervical cancer, with major potential impact, especially in resource-poor settings.
Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy ...(aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base.
Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis.
We identified 3075 patients with a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range IQR 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio HR 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779).
Patients with vulvar squamous cell carcinoma and positive surgical margins derive an OS benefit from aRT with a seemingly optimal dose in the range of 54.0 to 59.9 Gy.
The aim of this study was to evaluate injection of a novel hydrogel (TraceIT; Augmenix, Waltham, MA) between the cervix, rectum, and bladder in female cadavers compared with, and in addition to, the ...current standard of gauze packing, for organ-at-risk sparing in cervical cancer brachytherapy planning.
This brachytherapy cadaver study used T2-weighted MRI and CT imaging to compare three scenarios: (1) gauze packing alone, (2) hydrogel injection placed in the cervical fornices and rectovaginal septum, and (3) gauze packing in conjunction with hydrogel injection. Hydrogel distribution was evaluated. Doses to 2 cm3 volumes (D2cc) for the rectum, bladder, and sigmoid were collected. Statistical significance (p < 0.05) was evaluated using a two-tailed paired t test.
Hydrogel was successfully injected to space the bladder and rectum from the cervix in all five cadavers. The spacer was easily identifiable on both CT and MRI. The use of hydrogel in addition to packing resulted in a 22% decrease in rectum D2cc dose (p = 0.02), a 10% decrease in bladder D2cc (p = 0.27), and no change in sigmoid D2cc dose. No difference was observed between hydrogel only vs. gauze packing only.
Our results revealed a significant clinically meaningful decrease in rectal D2cc associated with the use of hydrogel in addition to gauze packing—TraceIT hydrogel holds promise as a spacer in cervical cancer therapy.
Despite its established efficacy, brachytherapy is underused in the management of cervical and vaginal cancers in some parts of the world. Possible reasons for the underutilization of brachytherapy ...include the adoption of less invasive techniques, such as intensity-modulated radiotherapy; reimbursement policies favoring these techniques over brachytherapy; poor physician or patient access to brachytherapy; inadequate maintenance of brachytherapy skills among practicing radiation oncologists; transitioning to high-dose-rate (HDR) brachytherapy with increased time requirements; and insufficient training of radiation oncology residents.
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