Rachelle M. Lanciano

Influence of age, prior abdominal surgery, fraction size, and dose on complications after radiation therapy for squamous cell cancer of the uterine cervix. A patterns of care study

The 1973 and 1978 national surveys conducted by the Patterns of Care Study (PCS) for squamous cell cancer of the uterine cervix were combined to analyze factors associated with complications after radiation therapy (RT). Overall, 1558 patients were reviewed, with a median follow‐up of 43 months. Major complications (defined as necessitating hospitalization for management) were seen in 152 of 1558 (9.8%) patients, with a 5‐year actuarial rate of 14%. A number of pretreatment and treatment factors were analyzed with respect to complications. In univariate analysis, significant pretreatment and treatment factors associated with an increase in complications included young age, prior laparotomy for staging, history of prior abdominal surgery, increasing stage, use of external RT, high fraction size, cesium source, and high para‐central (PCS point A) and lateral (PCS point P) doses. Multivariate analysis showed a history of prior abdominal surgery, paracentral dose greater than 7500 cGy, use of cesium, daily fraction size greater than 200 cGy, and age younger than 40 years to be associated independently with complications. A detailed analysis of the type of and time to complications is presented. The knowledge and skillful management of these pretreatment and treatment factors may improve the therapeutic ratio for RT, which is the most active curative modality against cervical cancer.

Decreasing gastrointestinal morbidity with the use of small bowel contrast during treatment planning for pelvic irradiation

Small bowel tolerance is a major dose-limiting factor in treating the pelvis with radiation therapy (RT). The use of small bowel contrast during RT simulation is one technique used to localize the bowel and identify the treatment plan that would exclude the greatest volume. To determine the influence of treatment planning with oral contrast on gastrointestinal injury, acute and chronic small bowel morbidity was analyzed in 115 patients with endometrial and rectal carcinoma who received postoperative radiation therapy at the Fox Chase Cancer Center. Mean and median time of follow-up were 31 and 27 months, respectively. Acute diarrhea was seen in 82% of the patient population. Ten percent of patients experienced major complications requiring hospitalization. Ninety-three percent of patients simulated without contrast experienced side effects compared to 77% of patients simulated with contrast (p = .026). There was an increased incidence of chronic complications in patients who were not simulated with contrast dye (50% vs 23%, p = .014). Median duration of minor side effects was 4 months for patients planned without oral contrast and 1 month for patients who had contrast at the time of simulation (p = .036). The superior aspect of the treatment field was determined to be at a more inferior location in patients simulated with contrast, thereby excluding small bowel from treatment. Seventy-four percent of patients simulated without contrast had the upper border of the field placed at the superior aspect of the sacroiliac joint or above, compared to only 40% of patients planned with oral contrast (p = .002). This study has demonstrated decreased complications (both overall and chronic) as well as a change in the location of the treatment field with the use of small bowel contrast. Multivariate analysis revealed that both the use of oral contrast (p = .026) and a lower superior border of the treatment field (p = .007) were predictive for fewer sequelae to RT, indicating that planning with contrast leads to changes in the technical delivery of RT other than field placement (e.g., block placement). The reduced incidence and duration of small bowel morbidity may be in part caused by alterations of the treatment plan made when the small bowel is visualized at the time of simulation. It is therefore recommended that oral small bowel contrast be used during treatment planning for pelvic irradiation.

Volumetric analysis of small bowel displacement from radiation portals with the use of a pelvic tissue expander

PURPOSE Many techniques and devices have been used in an attempt to minimize gastrointestinal morbidity of pelvic irradiation. The value of a temporary intrapelvic tissue expander to displace small bowel from pelvic radiotherapy fields was analyzed by comparing volumetric treatment parameters of patients with and without such a device. METHODS AND MATERIALS Between 1983 and 1991, 77 patients with a diagnosis of endometrial (n = 35), colorectal (n = 41), or anal carcinoma (n = 1) received adjuvant postoperative radiotherapy after undergoing treatment planning simulation with the use of small bowel oral contrast medium. Fourteen of these patients underwent surgical placement of a temporary intrapelvic tissue expander prior to radiotherapy, and 63 patients did not. Small bowel volume within the treatment portals was measured for both initial pelvic and conedown fields for all cases, and compared between the two patient groups. RESULTS The volume of small bowel within the initial pelvic fields receiving full dose irradiation was significantly less among patients with a tissue expander. For patients with a tissue expander, mean volume receiving full dose irradiation was 25 cm3 (median 0 cm3, range 0-297 cm3), whereas the corresponding volume was 239 cm3 (median 181 cm3, range 0-943 cm3) without a tissue expander (p < .0001). A similar reduction of irradiated small bowel volume was noted in the conedown fields with the use of a tissue expander (p = .07). Volumes receiving less than full dose irradiation were also less within the initial pelvic (p = .0001) and conedown (p = .002) fields with a tissue expander. Multivariate analysis of patient and treatment-related parameters showed the use of a tissue expander to be the only factor correlated with decreased small bowel volume within the treatment field (p = .003). Morbidity related to placement and removal of the tissue expander was acceptable. Acute radiation-related morbidity was significantly less in patients irradiated with a tissue expander in place (p < .001). CONCLUSIONS Placement of an intrapelvic tissue expander was correlated with decreased small bowel volume within the radiotherapy treatment field. Diminished radiation-induced acute gastrointestinal morbidity was noted with use of a tissue expander.

The efficacy of cranial irradiation in ovarian cancer metastatic to the brain: Analysis of 32 cases

Objective To determine the role of irradiation in the management of brain metastases from epithelial ovarian cancer. Methods Tumor registries from five university cancer centers were searched to identify ovarian cancer patients with brain metastases. During a 30-year period (1965–1994), 4027 ovarian cancer patients were evaluated, 32 of whom were found to have cerebral metastases. Each received fractionated whole-brain irradiation (median dose 30 Gy, range 20–52.5). Five patients received concomitant chemotherapy with whole-brain irradiation. Results The median survival time for the whole population was 4 months. For the entire series, symptomatic response (complete response and partial response) was achieved in 23, 16 of whom were palliated until death. Patients with higher Karnofsky performance status (70 or above versus below 70) were more likely to derive a palliative response and attained a statistically significant survival advantage. No other factor predicted the likelihood of deriving a palliative response or a survival advantage after treatment. Conclusions In this large review of patients with cerebral metastases from ovarian cancer, we found that most of those treated with whole-brain irradiation achieved palliation until death. Nearly all women with high performance status derived durable palliation from cerebral irradiation. Wholebrain irradiation was an effective means of palliating ovarian cancer metastatic to the brain and provided a favorable alternative to other means of management.

Combined modality treatment for carcinomas of the uterine cervix and vulva.

Several attempts have been made during the preceding year to apply multimodality approaches to the treatment of carcinomas of the uterine cervix and the vulva. Neoadjuvant chemotherapy may render more cervical tumors resectable, but it does not necessarily improve curability when compared with similarly staged patients treated with definitive pelvic irradiation alone. Neither concurrent chemoradiotherapy nor adjuvant chemotherapy following hysterectomy have been shown to be superior to definitive radiotherapy in prospective randomized trials of cervical cancer patients. Exciting data continue to be reported for the integration of chemotherapy, radiotherapy, and conservative surgery in the management of vulvar cancer. Such initiatives are contingent on the close cooperation of oncologists during the design and implementation of prospective trials.

Survival and Control Prognosticators of Recurrent Gynecological Malignancies of the Pelvis and Para-aortic Region Treated with Stereotactic Body Radiation Therapy

Purpose To define prognostic factors associated with improved survival and local control (LC) for gynecologic cancer recurrences limited to the pelvis and para-aortic (PA) region using stereotactic body radiation therapy (SBRT). Methods Between 2/2008 and 7/2014, 30 women (35 targets) with pelvic or PA recurrence of endometrioid (n = 12), cervical (n = 11), ovarian (n = 3), uterine-serous (n = 2), or carcinosarcoma (n = 2) cancer were treated with SBRT. Eleven recurrences were located in the central pelvis, 11 along the pelvic sidewall (PSW), and 13 in the PA region. Results Five-year survival for all patients was 42% with a median survival of 43.4 months. Multivariate analysis revealed better performance status (PS), and smaller clinical tumor volume was significant for improved survival (p < 0.05). Conclusion SBRT is a local therapy for recurrent gynecological malignancies in the pelvis and PA region with curative potential. SBRT is especially effective for LC when targeting PSW or PA recurrence and for patients with a cervical/endometrioid uterine primary. Survival is improved for patients with better PS and smaller recurrence volume prior to SBRT.

Propensity Score Matched Comparison of Intensity Modulated Radiation Therapy vs Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Survival Analysis from the National Cancer Database

Purpose No direct comparisons between extreme hypofractionation and conventional fractionation have been reported in randomized trials for the treatment of localized prostate cancer. The goal of this study is to use a propensity score matched (PSM) analysis with the National Cancer Database (NCDB) for the comparison of stereotactic body radiation therapy (SBRT) and intensity modulated radiation therapy (IMRT) for organ confined prostate cancer. Methods Men with localized prostate cancer treated with radiation dose ≥72 Gy for IMRT and ≥35 Gy for SBRT to the prostate only were abstracted from the NCDB. Men treated with previous surgery, brachytherapy, or proton therapy were excluded. Matching was performed to eliminate confounding variables via PSM. Simple 1–1 nearest neighbor matching resulted in a matched sample of 5,430 (2,715 in each group). Subset analyses of men with prostate-specific antigen (PSA) > 10, GS = 7, and GS > 7 yielded matched samples of 1,020, 2,194, and 247, respectively. Results No difference in survival was noted between IMRT and SBRT at 8 years (p = 0.65). Subset analyses of higher risk men with PSA > 10 or GS = 7 histology or GS > 7 histology revealed no difference in survival between IMRT and SBRT (p = 0.58, p = 0.68, and p = 0.62, respectively). Variables significant for survival for the matched group included: age (p < 0.0001), primary payor (p = 0.0001), Charlson/Deyo Score (p = 0.0002), PSA (p = 0.0013), Gleason score (p < 0.0001), and use of hormone therapy (p = 0.02). Conclusion Utilizing the NCDB, there is no difference in survival at 8 years comparing IMRT to SBRT in the treatment of localized prostate cancer. Subset analysis confirmed no difference in survival even for intermediate- and high-risk patients based on Gleason Score and PSA.

Radiotherapy for gynecologic malignancies.

This review highlights the curative potential of radiation in gynecologic malignancies. The controversies concerning the role of surgery in the management of bulky cervical cancer is discussed. Prognostic factors associated with improved pelvic control with radiation alone are described, particularly the bulk of pelvic disease, which is not accounted for in the current International Federation of Gynecology and Obstetrics staging system. The potential for integration of radiation and chemotherapy into the management of vulvar cancer to improve cosmesis and function as well as to reduce the risk of locoregional recurrence is described. The role of whole abdominal radiation in the management of advanced endometrial and ovarian cancers as well as the role of hyperfractionation to reduce acute morbidity of large abdominal fields is reviewed. Prognostic factors associated with locoregional and distant failure for endometrial cancer are outlined and the new pathologic staging system is critically analyzed. Finally, the treatment of vaginal cancer with radiation alone (external beam plus interstitial-intracavitary radiation) or surgery is reviewed and the prognostic importance of the present modifications to the vaginal staging system are emphasized.

A “Red Shell” concept of increased radiation damage hazard to normal tissues just outside the PTV target volume

To the Editor New methods of radiation dose delivery – SBRT, Cyberknife, Protons, Tomotherapy, Rapid Arc – can deliver large doses per fraction, which includes a zone or shell of potentially damaged tissue just outside the PTV, before the dose has fallen to a low enough dose to be regarded as ‘‘safe’’ for normal tissues. Doses prescribed as 3 20 Gy, 4 15 Gy or 5 12 Gy deliver EQDs at the PTV border of 275, 216 or 180 Gy EQD, respectively which are 2–4 times greater doses than any known to be tolerable to normal tissues. [EQD means equivalent dose in 2 Gy fractions, assuming alpha/beta = 3 Gy for late complications]. It may be many mm outside the PTV before these doses fall to the 70 or 80 Gy EQD, or less, that are known to be tolerable, with volume limitation, from conventional radiotherapy experience. We have found it useful in treatment planning to designate these danger zones clearly by a zone of red color in the Planning Program, which we call the Red Shell. The upper dose limit is the boundary of the CTV. The space between the CTV and the PTV is called the Inner Red Shell, which probably contains some tumor cells. The Outer Red Shell is between the PTV border and the arbitrary lower isodose that we decide is a ‘‘tolerance dose surface’’ for each individual treatment plan. Much consideration is necessary in deciding at which dose level that lower isodose level should be set. That ‘‘consideration process’’ is the first useful aspect of the Red Shell concept. It might be as high as 70 Gy EQD, or as low as 20 Gy EQD for certain radiosensitive tissues. In parallel-structure tissues it is higher for smaller volumes, e.g. 80 Gy EQD in 2 cc. The thickness and volume of a Red Shell can be used as measures of how good a given variant of the plan might be; first purely visually, and then if necessary in terms of volume in cc or thickness in mm. For various normal tissues in proximity to the PTV, the problem is difficult, but the exercise leads to learning and sharing of information. We suggest that other groups might like to try this approach to the problem of high risk to normal tissues close to PTV target volumes during the planning of treatments. We are preparing further reports of our own experience.

37 The relationship of local and distant failure from endometrial cancer: Defining a clinical paradigm

Purpose. Recently, statistical methods have been developed to rigorously assess the relationship between local and distant failures. Such methodology has successfully been applied to a variety of tumors including those arising in the prostate, breast, and cervix. To date, no published data are available to generate a hypothesis to characterize the relationship between local and distant failure for endometrial cancer. The present analysis was undertaken to determine the effect of locoregional control on subsequent metastatic dissemination among women with pathologically staged endometrial cancer treated by hysterectomy followed by adjuvant radiotherapy. Methods. The series consisted of 394 patients with FIGO stages I-III endometrial cancer who were surgically staged prior to irradiation [median external beam dose 45 Gy ± brachytherapy (median vaginal surface dose, 30 Gy)]. The duration of follow-up ranged from 2 to 151 months, with a median of 62 months. Multiple factors were evaluated to determine the associations with distant relapse including FIGO pathological stage, grade, histopathologic subtype (adeno vs papillary/papillary-serous/clear cell), depth of myometrial penetration, age, and local disease status. Time-dependent survival models were generated to assess the influence of local failure on distant metastases. Results. For the entire series, the 5-year actuarial rates of local and distant failures were 9 and 20%, respectively. Women who failed locally had nearly a fourfold risk of failing distantly compared to those who remained locally controlled (P = 0.02). Moreover, the earlier a local failure developed (e.g., within 1 year vs within 3 years), the more likely it was to be associated with distant metastases (P < 0.05). The univariate correlations of other factors with the 5-year rate of freedom from distant relapse also disclosed significant associations for grade, histology (adenoca vs papillary/ papillary-serous/clear cell), and FIGO path stage. In multivariate analysis, only local control, low grade (grade 1 and 2), and early pathological stage were independently related to the likelihood of achieving freedom from distant relapse. Conclusions. Distant dissemination of endometrial cancer may develop secondary to local failure. Optimization of local control is therefore necessary if long-term cure is to be achieved. The limits of the current database cannot establish whether local failure is a cause of distant spread or a high-risk marker for metastases; however, ongoing national cooperative trials may resolve this controversy.