Caroline L. Holloway

Intervals Longer Than 20 Weeks From Breast-Conserving Surgery to Radiation Therapy Are Associated With Inferior Outcome for Women With Early-Stage Breast Cancer Who Are Not Receiving Chemotherapy

PURPOSE To determine the interval from breast-conserving surgery (BCS) to radiation therapy (RT) that affects local control or survival. PATIENTS AND METHODS The 10-year Kaplan-Meier (KM) local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and breast cancer-specific survival (BCSS) were computed for 6,428 women who had T1 to 2, N0 to 1, M0 breast cancer that was diagnosed in British Columbia between 1989 and 2003, and who were treated with BCS and RT without chemotherapy. Intervals from BCS to RT were grouped by weeks as follows: < or = 4 (n = 83), greater than 4 to 8 (n = 2,288; reference group); greater than 8 to 12 (n = 2,606); greater than 12 to 16 (n = 961); greater than 16 to 20 (n = 358); and greater than 20 weeks (n = 132). Cox proportional hazards models and matching were used to control for confounding variables. RESULTS The median follow-up time was 7.5 years. The 10-year KM outcomes were as follows: LRFS, 95.4%; DRFS, 90.5%; and BCSS, 92.5%. Compared with the greater than 4 to 8 weeks group, hazard ratios (HR) were not significantly different for any outcome among patients who were treated up to 20 weeks after BCS. However, LRFS (hazard ratio [HR], 2.00; P = .15), DRFS (HR, 1.86; P = .02) and BCSS (HR, 2.15; P = .009) were inferior for women with BCS-to-RT intervals greater than 20 weeks compared with those greater than 4 to 8 weeks. The matched analysis yielded similar results. CONCLUSION Outcomes were statistically similar for BCS-to-RT intervals up to 20 weeks, but they were inferior for intervals beyond 20 weeks. Time can be reasonably allowed for the breast to heal and for patients to consider treatment options, but RT should start within 20 weeks of BCS.

Sigmoid dose using 3D imaging in cervical-cancer brachytherapy ☆

BACKGROUND AND PURPOSE To evaluate the proximity, variance, predictors of dose, and complications to the sigmoid in cervical-cancer brachytherapy using 3D planning. MATERIALS AND METHODS Over 36 months, 50 patients were treated for cervical cancer with either low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy. The distance from the central tandem to the sigmoid, the D0.1 cc and the D2 cc to the sigmoid, rectum and bladder doses, and toxicity were analyzed. RESULTS The median sigmoid EQD2 D0.1 cc and D2 cc were 84 Gy and 68.3 Gy for HDR versus 71.1 Gy and 65.9 Gy for LDR (p=0.02 and 0.98, respectively). Twenty percent of the HDR fractions required manipulation of the superior dwell positions to decrease the sigmoid dose. The median distance from the sigmoid to the tandem was 1.7 cm (range [rg], 0.1-6.16 cm) for HDR and 2.7 cm (rg, 1.17-4.52 cm) for LDR; from the sigmoid to the 100% isodose region the median distances were -0.1 cm (rg, -1.4 to 2.5 cm) and 0.44 cm (rg. -0.73-5.2 cm), respectively. The proximity of the sigmoid to the tandem is significantly related to sigmoid dose (p<0.0001). Within-patient (among-fraction) variation in sigmoid-to-tandem distance during HDR was substantial (coefficient of variation =40%). No grade 3-4 sigmoid toxicity was seen after a median 31-month follow-up period. CONCLUSIONS 3D imaging in cervical-cancer brachytherapy shows the sigmoid in close proximity to the tandem. The sigmoid-to-tandem distance varies substantially between fractions, indicating the importance of sigmoid dose-volume evaluation with each fraction.

Should the organs at risk be contoured in vaginal cuff brachytherapy

PURPOSE To assess the dose to the organs at risk (OARs) and utility of repeated OAR dose-volume histogram calculations in multifraction high-dose-rate vaginal cylinder brachytherapy using 3-dimensional imaging. METHODS AND MATERIALS Thirty-eight patients (125 fractions) received high-dose-rate brachytherapy to the vaginal vault between January 2005 and October 2005. All patients emptied their bladders before insertion. After each insertion, a CT scan with 2.5-mm slices and contours of the bladder, rectum, and sigmoid was performed. Dose-volume histograms were generated for the D(0.1cc) and D(2cc) for the OAR using a software program created at our institution. Variance component models estimated the within-patient variance of the dose to the OAR between fractions. Predictors of dose to the OAR were identified using linear mixed models. RESULTS The within-patient coefficients of variation of total D(0.1cc) dose were bladder 14.0%, rectum 7.9%, and sigmoid 27.6%; for D(2cc), these were 8.1%, 5.9%, and 20.3%, respectively. Intraclass correlations ranged from 0.27 to 0.79. Larger OAR predicted greater total D(0.1cc) and D(2cc). Other predictors of total D(0.1cc) and D(2cc) dose included the size of the cylinder and the length of the treatment field for rectum. CONCLUSIONS CT simulation provides a noninvasive assessment of the dose to the bladder, rectum, and sigmoid. The small within-patient variation in doses to the bladder and rectum do not support reporting doses to the OARs beyond the initial fraction.

American Brachytherapy Society (ABS) consensus statement for sarcoma brachytherapy.

PURPOSE To present recommendations for the use of brachytherapy (BT) in patients with soft tissue sarcoma (STS). METHODS A group of practitioners with expertise and experience in sarcoma BT formulated recommendations for BT in STS based on clinical experience and literature review. RESULTS The indications for adjuvant BT are discussed. There is no consensus on the use of BT alone or in combination with external beam radiation therapy (EBRT), but factors that influence the selection of this modality include tumor grade and size, prior surgeries, and tumor recurrence. Low-dose-rate, high-dose-rate, and pulsed-dose-rate radiation are all acceptable BT modalities to use for STS. Recommendations are made for patient selection, techniques, dose rates, and dosages. Outcome data and toxicity data are reviewed. CONCLUSIONS BT is a useful component of the treatment of STS. The advantages of BT are the targeted dose distribution, low integral dose, and short treatment times. Ultimately the clinician should select the modality or combination of modalities that are most familiar to the treatment team and suitable to the patient.

Intraoperative seed placement for thoracic malignancy—A review of technique, indications, and published literature

PURPOSE This review examines the role of permanent radioactive seed implantation in thoracic malignancy. This technique can be used intraoperatively to provide additional highly localized radiation therapy in cases where optimal oncologic margins are unattainable or to palliate unresectable disease. METHODS AND MATERIALS Relevant trials were identified through a systematic literature search using Pubmed. RESULTS The intraoperative placement of brachytherapy seeds has been described after sublobar resection for non-small-cell lung cancer (NSCLC), where surgical margins are close or microscopically positive and in the presence of macroscopic residual disease. This brachytherapy technique is currently the focus of a randomized prospective trial in the USA in patients unfit for lobectomy for early-stage NSCLC. CONCLUSIONS This review summarizes the methods of brachytherapy seed placement and the published experience of brachytherapy implants within the thorax, also examining radiation safety and postoperative dosimetry. This technique has the potential to improve local control with optimal sparing of normal tissue owing to its highly conformal radiotherapy delivery.

Three-Arm Randomized Phase III Trial: Quality Aloe and Placebo Cream Versus Powder as Skin Treatment During Breast Cancer Radiation Therapy

BACKGROUND The efficacy of aloe extract in reducing radiation-induced skin injury is controversial. The purpose of the present 3-arm randomized trial was to test the efficacy of quality-tested aloe extract in reducing the severity of radiation-induced skin injury and, secondarily, to examine the effect of a moist cream versus a dry powder skin care regimen. MATERIALS AND METHODS A total of 248 patients with breast cancer were randomized to powder, aloe cream, or placebo cream. Acute skin toxicity was scored weekly and after treatment at weeks 1, 2, and 4 using a modified 10-point Catterall scale. The patients scored their symptom severity using a 6-point Likert scale and kept an acute phase diary. RESULTS The aloe formulation did not reduce acute skin toxicity or symptom severity. Patients with a greater body mass index were more likely to develop acute skin toxicity. A similar pattern of increased skin reaction toxicity occurred with both study creams compared with the dry powder regimen. CONCLUSION No evidence was found to support prophylactic application of quality aloe extract or cream to improve the symptoms or reduce the skin reaction severity. Our results support a dry skin care regimen of powder during radiation therapy.

Successful treatment of non-Hodgkin lymphoma associated immune thrombocytopenia with involved field radiotherapy

Immune thrombocytopenia complicates the course and impacts the outcome of non‐Hodgkin lymphoma (NHL‐ITP, non‐Hodgkin lymphoma–immune thrombocytopenic purpura). The response to corticosteroids and/or intravenous immune globulins is usually short lasting, but NHL‐ITP usually responds to anti‐lymphoma chemotherapy. It is not clear if this success is due to the elimination of the lymphomatous tissue or to the immunosuppressor/immunomodulator effect of chemotherapy. Myelosuppressive anti‐lymphoma chemotherapy carries the risk of severe thrombocytopenia that may not respond adequately to platelet transfusion support. We report on a patient with recurrent diffuse large B‐cell lymphoma that coincided with immune thrombocytopenia. Both diseases completely responded to involved field radiation therapy. This supports the hypothesis that at least in some cases of NHL‐ITP, the lymphomatous clone secretes the anti‐platelet antibodies. This supports the therapeutic decision making for these patients. Copyright

Stage IIIC Endometrial Cancer: Relapse and Survival Outcomes in Women Treated With Pelvic or Extended Field Para-Aortic Nodal Radiation Therapy.

Purpose: The optimal radiation (RT) volume for node-positive endometrial cancer is controversial. This study evaluates clinical outcomes in patients with stage IIIC, N1 endometrial cancer who received RT to the pelvis (PV RT) or pelvis plus para-aortic nodes (PV-PAN RT). Methods: Overall, there were 89 women with stage IIIC endometrial cancer. Of these, 57 women had N1-only disease, forming the study cohort. Clinicopathologic characteristics, recurrence rates, endometrial cancer–specific survival (ECSS), and overall survival (OS) were examined among patients treated with pelvic RT (n=23) compared with pelvic plus para-aortic RT (n=34). Multivariable analysis of ECSS and OS was performed using Cox regression modeling. Results: Median follow-up was 5.1 years. Adjuvant chemotherapy was used in 51/57 (89%) of N1 cases. Women with N1 disease who received PV-PAN RT compared with PV RT experienced lower recurrence (26% vs. 52%, P=0.06) and higher survival rates (5 y ECSS 81.5% vs. 47.0%, P=0.04 and OS 79.1% vs. 47.0%, P=0.01). On multivariable analysis, RT volume was not significantly associated with OS, whereas chemotherapy was associated with improved ECSS and OS. Conclusions: RT conferred excellent local control, whereas chemotherapy was associated with improved survival in women with N1 endometrial cancer. Distant relapse remains the most common site of recurrence despite chemotherapy.

Postoperative Vaginal Cylinder Brachytherapy in an Era of 3D Imaging

Postoperative adjuvant intravaginal brachytherapy (VBT) is frequently used in the treatment of post-hysterectomy endometrial cancer. The dose prescription point and treatment length vary between institutions. The bladder, rectum and sigmoid (organs at risk, OAR) are in the immediate vicinity of the brachytherapy dose and can be visualized at the time of simulation. Imaging with either 2D or 3D techniques allows for verification of applicator size, placement and doses to the OAR. 3D imaging also allows for verification of apposition of the apparatus to the vaginal walls and evaluates the dose to the OAR in a non-invasive manner. The use of 3D imaging and new applicators may permit dose sculpting in complex cases to cover the CTV or reduce dose to the OAR.

15: Feasibility of Collecting Patient Reported Outcomes for Patients Receiving Curative Intent RT for Gynecological Malignancies

CARO 2016 _________________________________________________________________________________________________________ was sent to all 14 provincial cancer centres in 2013. The survey included 72 questions in four different categories: general/demographic, pre-treatment assessment, EBRT and BT questions. Results: The response rate was 100%. Ten out of 14 centres treated cervical cancer patients and had a dedicated brachytherapy suite. All 10 centres that treated cervix cancer had a peer review process for quality assurance (QA). Nine centres had written treatment planning and delivery protocol and five centres used a specific plan evaluation protocol for organs at risk for EBRT. The standard EBRT technique was 4-field box in eight centres and one centre used IMRT if treating the para-aortic nodes simultaneously; one centre did not respond. The dose/fractionation scheme to the whole pelvis was 45-50 Gy in 1.8-2 Gy per fraction in all but one centre. Nine centres used image verification at some point during EBRT. All ten centres used HDR brachytherapy and one centre also used PDR brachytherapy to treat cervix cancer patients. Brachytherapy was performed under general anesthesia, regional anesthesia and conscious sedation in four, one and five centres, respectively. Only one centre offered interstitial brachytherapy. The majority of centres (eight of 10) used ultrasound image guidance for intrauterine applicator insertion. For treatment planning two centres used CT and MRI, four centres used CT only and four centres used orthogonal x-rays. GEC-ESTRO guidelines were used in three centres for target volume delineation and in five centres for organs at risk (OAR) dose constraints. Nine centres prescribed and reported dose to Point A. Volumetric dose prescription was performed in one centre and four centres reported dose to a target volume. Eight centres reported dose to OARs. The number of BT applicator insertions varied significantly between the centres ranging from one to six. The dose prescription was also variable ranging from 5.5 Gy to 8 Gy per fraction. Conclusions: The main findings from the survey were the variation in the BT dose fractionation and treatment planning used in the regional cancer centres while there was a general uniformity in peer reviewed QA, written institutional treatment protocol, EBRT technique, dose fractionation scheme and use of HDR BT across the province. This study shed light on the need to implement a harmonized evidence-based brachytherapy practice for cervical cancer in order to improve patients’ outcome across Ontario, Canada.