Objective To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT). Population Large high risk clinical target volume (HR-CTV) volume (>40cc) at the time of brachytherapy cervical cancer patients were recruited. Methods This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemo-radiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) with cisplatin chemotherapy treated before IC/IMRT. The prescription dose for HR-CTV and IR-CTV were 6 Gy and 5 Gy per fraction for 5 fractions respectively. Results: Mean HR-CTV was 65.8±23.6 cc at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7±3.6 Gy and 78.1±2.5 Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8±3.8 Gy, 64.6±4.9 Gy, 63.9±5.3 Gy and 56.7±8.7 Gy respectively. Median follow-up was 85 months (47.9-124.2 months). Five-year local recurrence free survival rate, metastasis recurrence free survival rate, disease free survival rate and cancer special survival rate were 87.6%, 82.4%, 70.9% and 76.3%, respectively. The grade 1+2 gastrointestinal and urinary late toxicities were 15.8% and 21.1%, while grade 3 late toxicities were 3.9% and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen. Conclusions: The combination of ICBT with an applicator-guided supplementary IMRT boost achieved an excellent local control and overall survival with low toxicity for bulky residual cervical tumor

Purpose This study aimed to explore the relationship between applicator surface dose and 5 mm-depth dose and to optimize both locations simultaneously for three most used cylinder sizes (2.5, 3.0, and 3.5 cm in diameter) in treating patients with endometrial adenocarcinoma. Materials and methods A total of 216 plans were created for each dose level and applicator size. For each dose level, four plans were created with single or double prescription doses. For plans with double prescription doses, the dose constraints were applied to all those points on the surface and 5 mm depth and optimize the two sites simultaneously. Results A dose table between surface and 5 mm depth and its fifth order polynomial mapping functions were established for each applicator size, so any prescribed dose at one site can find the prescription dose on the other site in optimization on both locations. For plans with a 5 mm-depth prescription, the maximum dose on the surface can be reduced from 145% to 133% if the surface prescription dose is also used; for plans with surface dose prescription, the minimum dose and mean dose can be improved by 2% if 5 mm-depth dose prescription is also used in optimization. Conclusion Dose table and their mapping functions between surface prescription dose and their corresponding 5 mm-depth doses were created. A new optimization method that uses two prescription doses on both surface and 5 mm-depth sites was proposed to reduce the hot dose on the surface and improve the cold dose at 5 mm depth.

Abstract Background Vaginal bleeding (VB) is common in women with gynecologic (GYN) malignancies. Radiation therapy (RT) is used for the definitive treatment of GYN cancers and palliation of bleeding. The historical dogma is that high dose-per-fraction radiation leads to more rapid bleeding cessation, yet there is scant data supporting this claim. We sought to examine the effect of RT fraction size on VB via retrospective analysis of patients receiving hypofractionated radiation (HFRT) compared to conventionally fractionated radiation (CFRT) for control of bleeding secondary to GYN malignancies. Methods We identified patients receiving external beam RT for continuous VB from GYN malignancy treated in our department from 2012 to 2020. RT was classified as HFRT (> 2.0 Gy/fx) or CFRT (1.8–2.0 Gy/fx). Demographic information, disease characteristics, and treatment details were collected. The primary endpoint was days from RT initiation until bleeding resolution. Characteristics between groups were compared via Fisher’s exact test. Time to bleeding cessation was assessed via Kaplan–Meier and log-rank test. Univariable and multivariable Cox-proportional hazards were used to identify factors associated with bleeding cessation. Results We identified 43 patients meeting inclusion criteria with 26 and 17 patients receiving CFRT and HFRT, respectively. Comparison of baseline characteristics revealed patients receiving HFRT were older (p = 0.001), more likely to be post-menopausal (p = 0.002), and less likely to receive concurrent chemotherapy (p = 0.004). Time to bleeding cessation was significantly shorter for patients receiving HFRT (log-rank p < 0.001) with median time to bleeding cessation of 5 days (HFRT) versus 16 days (CFRT). Stratification by dose-per-fraction revealed a dose–response effect with more rapid bleeding cessation with increased dose-per-fraction. While HFRT, age, recurrent disease, prior pelvic RT, and prior systemic therapy were associated with time to bleeding cessation on univariable analysis, HFRT was the only factor significantly associated with time to bleeding cessation in the final multivariable model (HR 3.26, p = 0.008). Conclusions Patients with continuous VB from GYN tumors receiving HFRT experienced more rapid bleeding cessation than those receiving CFRT. For patients with severe VB, initiation of HFRT to control malignancy related bleeding quickly may be warranted.

PURPOSE:This study aimed to report the early toxicity results of a prospective clinical trial of prostate stereotactic body radiation therapy (SBRT) to the entire prostate with a simultaneous integrated boost (SIB) to magnetic resonance imaging (MRI)-defined focal lesions.METHODS AND MATERIALS:Eligible patients included men with biopsy-proven prostate stage T1c to T2c adenocarcinoma, a Gleason score ≤7, and prostate-specific antigen values of ≤20 ng/mL, who had at least 1 focal lesion visible on MRI and a total prostate volume no greater than 120 cm3. SBRT consisted of a dose of 36.25 Gy to the entire prostate with an SIB of 40 Gy to the MRI-defined lesions, delivered in 5 fractions. The primary purpose of the study was to confirm the feasibility of treatment planning/delivery and to estimate the rate of urinary retention requiring placement of a Foley catheter within 90 days of treatment. This study was to be considered successful if urinary retention occurred in no more than 15% of cases, with a planned enrollment of at least 25 patients.RESULTS:A total of 26 men were enrolled, and all underwent SBRT as planned. Twenty patients (77%) had intermediate-risk features, and the remainder were low risk. A treatment plan that met the protocol-defined goals for all cases was developed. Two patients (7.7%) developed acute urinary symptoms that required the temporary placement of a Foley catheter. No grade 3+ toxicity events were observed.CONCLUSIONS:Planning and delivery of prostate SBRT with a whole prostate dose of 36.25 Gy and a focal 40 Gy SIB is feasible. Early follow-up suggests that this treatment is not associated with undue morbidity.

The purpose of study is to measure Point A pear-shaped isodose dimensions of the conventional intracavitary brachytherapy with various sizes of colpostats and analyze which size of tumor is the optimal for 3-D interstitial brachytherapy. CT simulation was performed with Fletcher type applicator using various sizes of colpostats (2.0, 2.5, and 3.0 cm diameter). The Manchester standard loading (dwell time) system was used to generate pear-shaped isodose envelopes with high-dose rate iridium-192 according to the colpostat sizes. The size of the pear-shaped envelope was measured at 5 different levels: A-level (center of the colpostats), B-level (top of the colpostats), C-level (between B and D), D-level (Point A), and E-level (1.0 cm above Point A). In this study, it was assumed that uterine tandem was located at the center of tumor. For width of pear-shape: At the A-level, 6.4, 7.3, and 8.0 cm for 2.0, 2.5, and 3.0 cm colpostats, respectively. At the B-level, 5.8, 6.4, and 6.8 cm for 2, 2.5, and 3.0 cm colpostats, respectively. At the C-level, 4.6, 4.8, and 4.8 for 2.0, 2.5, and 3.0 cm colpostats, respectively. At the D-level, 4.0 cm for all different size. At the E-level, 3.8 cm for all 3 different size colpostats. A-level was the largest dimension of pear-shape. However, it was located in the upper vagina below the main cervical mass. The center of the effective pear-shape size for tumor was between the C and D levels. For thickness, all 5 different levels were ranging 3.7 to 4.0 cm. For height, the length of height was dependent on the tandem length. Therefore, the pear-shape envelope was able to accommodate up to 4.0 cm diameter volume. According to our analysis of conventional pear-shape dimension, 3-D interstitial brachytherapy should be considered for tumors larger than 4.0 cm for symmetrical tumor.

ObjectiveTo evaluate the incidence and risk factors for mesorectal node metastasis (MRNM) in locally advanced cervical cancer.Methods/MaterialsWe performed an observational retrospective cohort study of 122 patients with cervical cancer who received definitive chemo-radiation treatment between December 2013 and June 2017 to evaluate the incidence of MRNM. Three diagnostic radiologists assessed all available pre-treatment images. In this study, the pelvic node metastasis was defined as ≥ 1.0 cm and MRNM as ≥ 0.5 cm for CT and MRI scans and as a maximum standardized uptake value of > 2.5 for PET/CT. The relationship of MRNM with FIGO stage, pelvic node metastasis, and mesorectal fascia involvement was evaluated.ResultsThe incidence of MRNM in all 122 patients was 8 (6.6%). However, in advanced stage (III– IV) patients, MRNM occurred in 4 of 39 (10.3%) compared with 4 of 83 (4.8%) in early stage (IB1–IIB) patients (p = 0.27). In patients with a positive pelvic node, MRNM occurred in 7 of 55 (12.7%) and 1 of 67 (1.5%) in those with negative pelvic node (p = 0.02). In addition, the incidence of MRNM was 3 of 9 (33.3%) in the presence of mesorectal fascia involvement and 5 of 113 (4.4%) among those without mesorectal fascia involvement (p = 0.013).ConclusionThis study indicates that pelvic node metastasis and mesorectal fascia involvement are high-risk factors for MRNM. Therefore, vigilance of reviewing images in the mesorectum for MRNM is necessary for high-risk patients.

The adrenal gland is a common site of metastatic disease given its rich vascular supply, most notably with non-small cell lung cancer (NSCLC) histology. Progression-free and overall survival improvements with treatment of oligometastatic sites of disease have piqued interest in aggressive local therapies for these "intermediate" disease states. Stereotactic Body Radiation Therapy (SBRT) deposits tumoricidal radiation doses within the target volume, with minimal exposure to nearby organs at risk. Therefore, SBRT is dosimetrically an ideal radiation modality to provide local control (LC) for metastases in periadrenal and adrenal sites. However, limited data exist supporting fractionated SBRT for metastases in these locations. This study investigates LC rates with fractionated SBRT targeting periadrenal and adrenal metastases. From 2010-2018, 33 patients with periadrenal or adrenal metastases and limited oligometastatic (<5 sites) disease were consecutively treated with SBRT at a single institution. 3 patients were excluded for limited imaging or follow up data after treatment. Patients' demographic, clinical, and treatment data were abstracted from their charts. Local and distant failures on imaging studies were recorded to evaluate disease control. Toxicity was scored using CTCAE v 4.0. Overall survival (OS), progression free survival (PFS), and local failure free survival (LFFS) were estimated by Kaplan-Meier methods. Impact of clinical and treatment variables were calculated using Kaplan-Meier statistics and compared with log rank tests. Thirty patients (8 female, 22 male) with various primary histologies (12 hepatocellular carcinoma; 4 NSCLC; 3 melanoma; 9 other) received fractionated SBRT for definitive treatment of their metastases. Prescription doses were 30-54 Gy in 3-5 fractions, with mean and median BED10 of 75.8Gy and 60 Gy, respectively (range 48-151.2 Gy). Treatment related toxicities were minimal, with grade 1 or 2 nausea in 12 patients, no grade 3 GI toxicity, and no renal toxicity. Local control (LC) was achieved at the treated site in 25 patients (83.3%), with a median LFFS not reached (mean of 41 months). Median PFS was 12.3 months and median OS was 19.7 months. Histology and maximum tumor size did not significantly impact oncologic outcomes. Treatment with immunotherapy showed a non-significant trend towards improving OS (p=0.138), with no impact on LC or PFS. BED10 above 80 Gy showed a non-significant trend towards improved LC (p=0.177), without improvement in OS or PFS. Fractionated SBRT provides excellent tumor control with minimal toxicity in peri-adrenal and adrenal gland metastases. Dose schedules with BED10 above 80 Gy should be considered for definitive therapy to provide optimal local control. With modern systemic treatments improving survival outcomes in patients with oligometastatic disease, this treatment approach warrants further investigation in appropriately selected patients.

Advanced imaging modalities have identified mesorectal nodal metastasis as a risk in locally advanced cervical cancer. Although controversial, recent contouring guidelines for IMRT recommend inclusion of mesorectum in high-risk patients. This study is to evaluate how much rectum and mesorectum receives the prescription dose for conventional 3D conformal RT (3D-CRT) and IMRT. Twenty previously irradiated intact cervical cancer were identified (Stage I: 10, Stage II: 4, Stage III: 6). The planning target volume was constructed by adding 2.0 cm margin to the gross tumor and uterus, 1.5 cm to the vagina, and 0.7 cm to the common, external and internal iliac, obturators and pre-sacral pelvic lymph nodes. The mesorectum was comprised of the portion of the rectum extending from the caudal aspect to where the sigmoid could be first visualized in the axial plane on CT scan. For 3D-CRT planning, a 4-field box was designed with appropriate dosimetric margin and the plan normalized such that 88-93% of the PTV received the prescription dose. For IMRT, a seven-field plan was optimized for conformity only and normalized so that the 100% of the dose matched the same volume covered in the 3D-CRT plan. The beam energy was 15 MV and the prescription dose was 45Gy. Rectum and mesorectum dose-volume histograms were compared between 3D-CRT and IMRT. The mean mesorectal and rectal volumes were 117cm3 (60.6 - 237 cm3) and 71cm3 (33 – 163 cm3) respectively. The mean volume of rectum receiving at least 95% of the prescription was 93.0 % (79.9 – 100%) and 82.2% (44.9 – 99.9%) for 3D-CRT and IMRT, respectively. The mean volume of mesorectum receiving at least 95% of the prescription was 90.7% (78.6 – 99.7%) and 78.8% (48.2 – 99.4%) for 3D-CRT and IMRT, respectively. Larger rectum volumes were observed to have a larger volume covered by prescription dose as a trend with either modality. When treating with either conventional 3D or IMRT, the mean rectal volume receive most of the prescription dose. Therefore, it is likely that inclusion of entire mesorectum within target volume would be tolerated and can be considered for patients with high-risk for mesorectal nodal metastasis.

To study the dose differences with more than one interstitial syed implants for patients with cervical and vaginal cancer with or without deformable image registration.

This study aimed to investigate the dynamics of the vaginal wall dose for interstitial brachytherapy (ISBT). A patient undergoing ISBT was selected as the patient case. The phantom case was generated to simulate the patient case in all regards with the exception of parallel needle positions. The vaginal wall was contoured as a 0.5-cm expansion around the vaginal surface of the obturator. The prescribed ISBT dose was 20 Gy in 4 fractions. Six treatment plans were generated by modifying relative dwell times and needle positions (DTNP). The volume of the vaginal wall receiving > 150% of prescription dose (V> 150%) and D2cc of the vaginal wall were compared among plans. The V> 150% was much larger in the patient case (49.3%) due to unparallel needles compared with the phantom case (14.3%) without modification (plan 1). Among the 6 plans, reduced dwell time (plan 3) and no dwell time (plans 5 and 6) on the vaginal surface needles had the lowest vaginal wall doses with the use of a central obturator needle in both cases. In comparison of patient case plans 1, 3, 5, and 6, V150% was 49.2%, 19.0%, 21.3%, and 28.7%, respectively, and D2cc was 41.15 Gy, 33.10 Gy, 36.51 Gy, and 34.37 Gy, respectively, which was limited around each loaded needle. Modification of DTNP is able to reduce the vaginal wall volume exceeding 150% of the prescription dose in the patient case. Understanding these dynamics of the vaginal wall dose will improve dose optimization of ISBT and may reduce vaginal morbidities.

Purpose/objective(s): To assess subcutaneous adipose tissue characteristics by computed tomography (CT) as potential imaging biomarkers predictive of biochemical recurrence in men with high-risk prostate cancer receiving radiotherapy (RT). Materials and methods: This retrospective study included men with high-risk prostate cancer (PSA > 20 ng/ml, Gleason score >= 8, or clinical extraprostatic extension) treated between 2001 and 2012. All patients received definitive, dose-escalated external beam RT along with a course of neoadjuvant, concurrent, and adjuvant androgen deprivation therapy (ADT). Each patient also had a treatment planning CT that included the L4-L5 vertebral interface and prostate specific antigen (PSA) measurements for at least 2 years following RT. The subcutaneous adipose tissue was contoured on a single axial CT slice at the level of L4-L5. The average CT attenuation, in Hounsfield units (HU), of the structure was calculated and defined as SAT(Hu). SAT(AREA) was defined as the cross-sectional area of the structure (in cm(2)) that was then normalized by the square of patient height. Biochemical failure (BF) was defined as a PSA rise of 2 ng/ml from the nadir. Freedom from BF (FFBF) was calculated from start time of ADT using the Kaplan-Meier method. Estimates of FFBF were stratified by SATHu and SAT(AREA) quartiles. Results: A total of 171 men met the inclusion criteria with a median follow-up of 5.6 years. The mean SAT(HU) (+/- standard deviation) was -99.2 HU (+/- 6.1 HU), and the mean SAT(AREA) was 93.2 cm(2)/m(2) (+/- 39.4 cm(2)/m(2)). The 5- and 8-year rates of FFBF across all patients were 81.5% and 73.5%, respectively. Patients in the lowest quartile of SAT(HU) experienced significantly higher FFBF compared to the other quartiles (Q4 vs. Ql, P = 0.017; Q4 vs. Q2, P = 0.045; Q4 vs. Q3, P = 0.044). No other differences in FFBF were observed between quartiles of SAT(AREA) or other quartiles of SAT(HU). Conclusion: Lower subcutaneous adipose tissue density was associated with a lower rate of BF following RT with ADT for men with high-risk prostate cancer. Further research is needed to elucidate the biological underpinnings of this clinical finding and the role adipose tissue plays in modulating oncologic behavior and outcomes. (C) 2017 Elsevier Inc. All rights reserved.

Conventional radiation fields for gynecologic malignancies include the primary tumor and regional lymph nodes in the pelvis. However, the mesorectum is not routinely assessed and usually is avoided to limit treatment related toxicities. There is a previous case report about mesorectal lymph node metastases (MRNM) in gynecologic cancers, but to the best of our knowledge there is no reported data evaluating the incidence of MRNM in this population. We would like to report our initial findings on MRNM incidence in cervical and vaginal cancer. A total of 31 patients sequentially evaluated for radiotherapy of cervical or vaginal cancer within the last year were reviewed. Three diagnostic radiologists retrospectively assessed all available pre-treatment imaging for positive nodal involvement in the pelvis, including the mesorectum. Pelvic nodal metastasis was defined as ≥ 1 cm, MRNM as ≥ 0.5 cm for CT and MRI scans. PET / CT scans generally were considered positive with SUV max > 2.5. The relationship of MRNM incidence with primary site, FIGO stage, other lymphatic involvement, and histology were evaluated. Of the 31 patients, 25 cervical (Stage IB2: 5; Stage II: 8; Stage III: 10; Stage IV: 2) and 6 vaginal (Stage I: 1; Stage II: 4; Stage III: 1) cases were evaluated. Eighteen pre-treatment PET/CT, 15 CT and 5 MRI scans were reviewed. Nineteen (61%) patients had positive pelvic nodal metastasis. Four of the 31 patients were positive for MRNM, which constitutes 12.9% of all the reviewed patients and 21% of patients with other pelvic nodal involvement. Of the patients with MRNM, two had cervical cancer (both stage III) and two had vaginal cancer (one stage II and one stage III). All patients with MRNM had squamous histology and had presence of pelvic node involvement. The incidence of MRNM was 12.9% of all reviewed patients and 21.0% of all patients with pelvic lymphatic involvement. More advanced disease and pelvic lymph node involvement are associated with MRNM. Further investigation is ongoing.

Ocular melanoma is a rare disease commonly treated with radiation therapy to preserve the eye. The purpose of this study was to describe local control and toxicity following Iodine-125 (I-125) plaque brachytherapy in a large, single-institution cohort of ocular melanoma. All patients who received I-125 plaque for non-metastatic ocular melanoma at a single institution from 2003 to 2012 were reviewed. Patients were excluded if treated with proton beam radiation therapy, laser therapy, or transpupillary thermotherapy (TTT) prior to or in combination with I-125 brachytherapy. Patients with detailed ophthalmic exams prior to treatment and post-treatment exams at 12 and 24 months were analyzed for the following: change in visual acuity (VA), cataract surgery, vitreous hemorrhage (VH), radiation retinopathy (RR), and enucleation. Local control (defined as lesion stable or regressed) and additional treatments delivered for ocular melanoma were also recorded. A total of 165 patients were treated. Of these, 107 had complete ophthalmic exams at baseline, 12 months, and 24 months. All patients had minimum follow up of 24 months. Median patient age at the time of I-125 was 66 years (range 39-93). Median tumor height was 4.88 mm (range 2-10.9 mm) and median plaque diameter was 16 mm (range 10-20 mm). The majority of patients (86%) were prescribed 80 Gy to tumor apex or 5 mm from sclera (if height less than 5 mm). The remainder received 65-75 Gy due to normal tissue constraints (sclera dose less than or equal to 450 Gy) and these all had tumor height of 8 mm or greater. The mean dose delivered to the apex and sclera was 96 Gy and 336 Gy, respectively. Local control at 24 months was 95%. The mean tumor height of those that failed was 8.2 mm. Secondary treatment for ocular melanoma was required in 24% of patients. Toxicity is shown in the table below. Visual acuity declined after 12 months of follow up and was significantly lower at 24 months when compared to baseline VA. Thirteen patients required enucleation, 9 (69%) for recurrence and 4 (31%) for toxicity. At 24 months, 11 patients (10.3%) required surgery for cataracts, 48 (45%) developed RR, and 15 (14%) developed VH. Of the patients who developed RR or VH, 15 (31%) and 4 (26.7%) required treatment, respectively.Abstract 2822; Table 1.Pretreatment (n = 107)12 month (n = 107)24 month (n = 107)Median VA20/4020/45 (P = 0.11, baseline)20/70 (P = 0.002, baseline)VA 20/50 or better51.4%55.1%37.4%VA 20/200 or better86.0%77.6%62.6%VH4.7%2.8%14.0%RRn/a17.8%44.9%Enucleationn/a5.6%12.4% Open table in a new tab Plaque brachytherapy is a safe and effective treatment for ocular melanoma. Local control is excellent at 2 years with low overall toxicity rates. However, greater tumor height was associated with a decrease in local control. There was no acute or dramatic change in VA, but VA continues to decline over the follow-up period with most patients maintaining functional vision.

Whole pelvic radiation therapy (WPRT) is an integral part of treatment for locally advanced cervical and vaginal cancer prior to brachytherapy. The most common beam arrangements for WPRT are opposed anteroposterior/posteroanterior beams and the 4-field box. The lateral fields of the 4-field box spare small bowel and a portion of the rectum from radiation. Intensity modulated radiation therapy (IMRT) is increasingly used for gynecologic (GYN) cancers to improve dose conformity.

Optimal brachytherapy applicator placement is important in improving local control and organ at risk (OAR) sparing in patients with cervical cancer. Criteria for proper placement have been described based on 2-dimensional imaging. In the era of 3-dimensional (3D) imaging, both International Commission on Radiation Units and Measurements (ICRU) reference points and minimum dose to 2 cc volume receiving the highest dose (D2cc) are used to evaluate post-implant dosimetry. The purpose of this study was to evaluate the impact of applicator position in the pelvis and patient anatomy on ICRU reference point dose and OAR D2cc using 3D imaging in cervical cancer patients. Forty-five thin-slice pelvic computed tomography (CT) scans from 15 patients with cervical cancer (1 IB1, 3 IB2, 1 IIA1, 3 IIA2, 6 IIB, and 1 IIIB) having 3 high-dose-rate ICBT applications of 8 Gy to point A following external beam radiation therapy (EBRT) were reviewed. Applicator consisted of Fletcher tandem and ovoids. Applicator geometry was evaluated using consensus guideline parameters. Anatomic parameters included uterus thickness and uterus and bladder volume. Dose to rectal (RP) and bladder (BP) ICRU reference point and physician-contoured OAR (bladder, rectum, small bowel, and sigmoid colon) D2cc were determined for each fraction. Mixed linear regression model with Bonferroni correction was used to determine the effect of applicator position and patient anatomy on OAR D2cc and ratio of OAR reference point dose and D2cc. Median tandem length, curvature, and ovoid size were 6 cm, 30 degrees, and 2.5 cm, respectively. Increased uterus volume decreased small bowel D2cc (P=.002). Increased uterus thickness decreased RP dose (P<.001) and bladder D2cc (P<.001). Increased rectal packing decreased RP dose (P<.001). Mean ratio of bladder point dose to D2cc was 0.76±0.39. Mean ratio of rectum point dose to D2cc was 1.21±0.58. Increased cranial distance of the applicator from symphysis pubis (distance from the flange to the top of the symphysis pubis) decreased BP dose (P<.001) and the ratio between BP and bladder D2cc (P<.001) without significantly changing bladder D2cc or any other organ dose. Posterior sagittal rotation of the applicator (distance from symphysis pubis to the tandem) decreased ratio of BP and bladder D2cc (P<.001) and increased ratio of RP and rectum D2cc (P=.001). This study confirms the importance of applicator geometry and its effect on point dose and D2cc. Increased cranial distance of the applicator from symphysis pubis significantly decreases the ratio between BP dose and D2cc without negatively impacting dose to other OARs. In addition, uterus size and shape have significant impact on both OAR reference point dose and D2cc.

The conventional pear-shaped isodose distribution achieved with tandem and ovoid intracavitary brachytherapy makes it the ideal treatment modality for cervical cancer. In patients with narrow vaginal vaults, the placement of tandem and mini-ovoid (TMO) has been commonly used due to anatomical factors that would prevent use of standard size ovoids. However, this may produce suboptimal tumor coverage for larger tumors. This study evaluates the outcomes of patients treated with TMO stratifying by size and volume of the residual tumor at the time of brachytherapy. Between 2008 and 2010, 98 patients with stage IB1 - IVA squamous cell carcinoma of the uterine cervix were treated with chemo-radiotherapy and high-dose-rate (HDR) tandem and ovoid brachytherapy. Of these, we identified 19 patients treated with the TMO intracavitary brachytherapy. All patients had a CT simulation at the time of the first implant. The CT-based residual tumor dimensions and high risk clinical target volume (HR-CTV) were defined at the time of first brachytherapy implant after completion of whole pelvis chemo-radiotherapy. CT-based residual tumor dimensions were defined as follows: the CTV width and thickness (CTVw and CTVt) were defined at the epi-center of the HR-CTV on the axial and sagittal plane. The CTV height (CTVh) was calculated as 1/3 of the whole uterus length due to poor visualization of the tumor on CT imaging. The HR-CTV structure was contoured to encompass the entire cervix (lower 1/3 of the uterus) plus any para-cervical residual tumor. The effect of size and volume of the HR-CTV on loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) was assessed using the Kaplan-Meier method and log-rank analysis. Median followup was 15 months. All patients received cisplatin based chemoradiation using 4 field whole pelvis technique to 45 Gy with a 5.4 Gy parametrial boost. Intracavitary brachytherapy was administered after completion of the external beam radiation therapy, as 24 Gy in 3 fraction except one patient who received 18 Gy in 2 fractions. One patient had stage IB1, 3 stage IB2, 3 stage IIA, 5 stage IIB and 7 stage IIIB. Eleven patients had TMO implants on all three procedures, with 8 patients having 2 out of the 3 implants being TMO. Prescription was to point A without the use image-guidance to optimize isodose curves. Median HR-CTVw was 5.6 cm, HR-CTVh 2.47 cm and HR-CTVt of 4.39 cm. The median HR-CTV volume was 45.44 cc. For the entire group, the actuarial 2-year LRC, DFS and OS was 75%, 59% and 63%,respectively. These results compare unfavorably with our previously reported outcomes of locally advanced cervical cancer patients, with 2-year LRC, DFS and OS of 81.5%, 74.9% and 91.3%, respectively. Statistical differences for LRC and DFS were seen with HR-CTV volumes >45 cc: 2-year LRC 88.9% vs 60% (p=0.061) and DFS 88.9% vs 50% (p = 0.019). On univariate analysis, the CTVh and CTVt were statistically significant for DFS (p=0.018 and p=0.041, respectively). CTVw and stage III trended towards significance (p=0.064 and p=0.291, respectively). Our results indicate that the use of TMO in patients with a narrow vagina and large residual tumor (HR-CTV >45cc), resulted in poor LC, DFS and OS in comparison to those with small residual tumor. Expansion of pear shape volumes via the use of interstitial brachytherapy may improve these results in this subset of patients.

To evaluate the dosimetric properties associated with urethral toxicities in patients treated with interstitial needle implantation as an adjuvant therapy to external beam radiation therapy in locally-advanced gynecologic malignancy. We retrospectively identified twenty-one patients treated in our department with high-dose-rate interstitial brachytherapy as an adjuvant therapy to pelvic external beam radiation therapy for locally advanced gynecologic malignancy. Ten patients had cervical cancer, nine patients vaginal cancer, one vulvar cancer, and one urethral cancer. Three patients had urethral involvement noted on physical examination and/or imaging prior to needle implantation. Nineteen of the patients received concurrent chemotherapy during external beam therapy which was most commonly cisplatinum. Patients were anesthetized with epidural anesthesia and Foley catheters were routinely inserted. All patients underwent three dimensional treatment planning with computed tomography. Treatment was completed with BrachyVision planning software and VariSource afterloading unit (Varian Medical Systems, Inc., Palo Alto, CA) using Iridium-192 sources. The urethra was identified via the Foley catheter which was contoured with a 2 mm margin to account for its epithelial lining. Mean and Dmax to the urethra were recorded and D0.1cc and D1cc was calculated with appropriate conversions to EQD2 using alpha-beta ratio of three. Mean urethral volume was 2.2 cc, with a range of 1.3 cc to 4.5 cc. Interstitial needle treatments were delivered twice daily with median dose of 24 Gy delivered in 4 fractions (EQD2 43.37 Gy in 4 fractions). In general, more fractions with a lower dose were delivered when distal vaginal involvement was present. External beam radiation therapy was most commonly a four-field technique with median dose of 45 Gy in 25 fractions. Six patients experienced grade 2 or higher urethral toxicity as graded by the common terminology criteria for adverse events v4.0 (CTCAE). One patient experienced a grade 3 urethrovaginal fistula that was also associated with a grade 2 urethral stricture requiring permanent suprapubic catheterization. One additional patient experienced a grade 2 urethral stricture but recovered following an indwelling Foley catheter present for two weeks. Two patients experienced grade 2 urinary incontinence requiring pad usage on a daily basis, and two experienced late grade 2 urinary frequency and dysuria without organic cause. There was a statistically significant increase in the Dmax to the urethra in patients with urethral involvement (9304 cGy vs. 7706 cGy, p=0.03) and a trend for increase in D0.1 cc (8287 cGy vs. 7326 cGy, p=0.07) but this did not persist for mean dose or D1cc. When the region of vaginal involvement (upper vs. lower) was compared to urethral dose, all dose parameters were significantly higher in patients with lower vaginal involvement. Dose comparisons for patients with no clinically significant toxicity versus those with grade 2 or grade 3 toxicity were done. Median D1cc and D0.1cc to the urethra associated with grade 2 toxicity was 6980 cGy and 7624 cGy, respectively. In our study, there was a 40% risk of grade 2 or higher urethral toxicity when dose to the urethra was above median doses listed above. No explicit dose response was found in relation to urethral toxicity, most likely because there were not a sufficient number of patients with high urethral dose. We feel grade 2 or higher toxicity may be related to D1cc > 7000 cGy or D0.1cc > 8000 cGy. Further data in patients with high urethral dosing will be needed to properly identify dose and volume responsible for urethral toxicity.

Three-dimensional image guided brachytherapy requires time-intensive treatment planning procedures after insertion of the applicator. We set out to quantify organ-at-risk (OAR) or applicator movement and dosimetric changes that may occur in the time between treatment planning and subsequent delivery of 3-D image guided high dose rate (HDR) intracavitary brachytherapy (IB) for cervical cancer. Eight consecutive patients underwent a total of 23 unique IB (Fletcher tandem and ovoids applicator) procedures for cervical cancer, with prescription of 8 Gy for each insertion. Following applicator placement, a treatment planning CT-sim was performed and a treatment plan was created/ approved. A second CT-scan was then performed immediately prior to treatment. The same bladder filling protocol was utilized for both scans. Each patient had applicator fixed to external clamp fixation device between and during scans. OAR volumes and D2cc values were recorded using the same treatment plan/dwell times for each insertion. To assess possible applicator movement, three measurements were taken on each scan: 1) distance between S1 vertebral body and top of the tandem; 2) distance from the flange on the tandem to the pubic symphysis; 3) distance between ovoids and cervical marker seeds. Statistical significance was evaluated by a paired samples t-test with two-sided significance testing. The mean time between CT-sim and pre-treatment CT scan was 74 mins (range 44-108). Table 1 shows a comparison of the mean OAR volumes, D2cc values, and applicator movement measurements. There was a small (4-6mm) but statistically significant movement of the applicator inferiorly based upon S1-tandem and flange-symphysis distance changes; however, there was no difference in distance from marker seed to ovoids. No significant D2cc changes for bladder, rectum, or bowel were noted. Though volume of sigmoid remained similar, statistically significantly different D2cc values were seen (571 vs 607 cGy). During treatment planning and patient transfer between CT scans, the Fletcher applicator and uterus may tend to move together slightly in the inferior direction. D2cc values did not change for bowel, bladder, or rectum. The sigmoid colon may have organ motion independent of the applicator, resulting in changes to sigmoid D2cc.Scientific Abstract 2658; TableComparison of mean values for CT-simulation and immediate pre-treatment CT-scansCT-simulationPre-Treatment CTP valueBladder Volume (cc)203.5213.7.09Rectum Volume (cc)66.163.8.17Sigmoid Volume (cc)65.265.5.94Bladder D2cc (cGy)724.1719.9.85Rectum D2cc (cGy)497.7463.5.12Sigmoid D2cc (cGy)607.0571.8.03Small Bowel D2cc (cGy)450.7423.2.18Tandem-S1 distance (cm)2.52.9.01Flange-pubic symphysis distance (cm)2.72.1.01Marker seed-ovoid distance (cm)0.650.66.85 Open table in a new tab

To investigate added morbidity associated with the addition of pelvic elective nodal irradiation (ENI) to hypofractionated radiotherapy to the prostate.