Component Of Local Failure Research Articles

Patterns of Prostate Cancer Recurrence After Brachytherapy Determined by Prostate-Specific Membrane Antigen–Positron Emission Tomography and Computed Tomography Imaging

The aim of this study was to characterize the patterns of prostate cancer recurrence after brachytherapy (BT) using 2-(3-[1-carboxy-5-([6-18F-fluoropyridine-3-carbonyl]-amino)-pentyl]-ureido)-pentanedioic acid ([18F]DCFPyL) prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and computed tomography (CT) imaging. Patients were selected from an ongoing prospective institutional trial investigating the use of [18F]DCFPyL PSMA PET and CT in recurrent prostate cancer (NCT02899312). This report included patients who underwent BT (either monotherapy or boost) and experienced a biochemical failure (BF) defined by the Phoenix definition (prostate-specific antigen [PSA] > 2 ng/mL above nadir). Between March 2017 and April 2020, 670 patients underwent [18F]DCFPyL PSMA PET and CT imaging. Of these 670 patients, 93 were treated with BT; 73 underwent monotherapy, and 20 underwent BT boost (19 low-dose rate and 1 high-dose rate). To report on patterns of recurrence outcomes, 86 patients (median prescan PSA 6.0) with a positive [18F]DCFPyL PSMA PET and CT scan and true BF were included. The most common location of relapse was local; 62.8% had a component of local failure (defined as prostate and/or seminal vesicles), and 46.5% had isolated local failure only, with no other sites of involvement. Regional failure occurred in 40.7% of patients, and 36.0% had metastatic failure. Isolated local recurrence was seen in 54.3% of monotherapy patients versus only in 12.5% of boost patients. Metastatic failure was seen in 28.6% of monotherapy patients versus 68.8% of the boost patients. Local recurrences (69.0%) were found within the same prostate biopsy sextant involved with the tumor at diagnosis, and 76.0% of patients with seminal vesicle recurrences had prostate-base involvement at diagnosis. Contrary to previous evidence, our study suggests that in prostate BT patients with biochemical recurrence, the most common site of failure is local for the patients treated with monotherapy and metastatic for patients treated with a combination of external beam radiation and BT boost.

Dosimetric predictors of local control and complications in gynecologic transperineal implant patients: The medical college of wisconsin experience

Investigate the relationship between dosimetric parameters with local control (LC) and complications following transperineal high-dose rate (HDR) interstitial brachytherapy (ISBT) for gynecologic (GYN) malignancies. Between 2001 and 2016, 59 patients were treated for primary or recurrent GYN malignancies. Most patients received external beam irradiation, followed by transperineal ISBT via the Syed-Neblett applicator set with CT-based planning. Treatment plans were retrospectively reviewed to evaluate for an association among LC or toxicity with the equivalent dose at 2 Gy per fraction (EQD2) for the clinical target volume (CTV), 0.1 cc (D0.1cc), and 2 cc (D2cc) volumes of the organs at risk (OAR), low/high dose volumes for the OAR and CTV, and ratio of dose at the core vs. the implant periphery. The median follow-up among survivors was 24 months. 34% of patients had a component of local failure and in 12%, this was isolated. Late grade 3 (G3) toxicity occurred in 15% of patients. There were no G4-5 toxicities. Rectal D0.1cc > 75 Gy trended toward significance in predicting the development of non-fistula late G2-3 rectal complications. Bladder D0.1cc > 94 Gy significantly predicted for the development of late G2-3 vesicovaginal fistula formation. The ratio of the total dose at the vaginal surface to the needle periphery above 121% trended in predicting for any complication or fistula formation. HDR ISBT combined with EBRT achieved LC in 66% of patients with advanced or recurrent GYN cancers. Rectal and bladder D0.1cc doses may be predictive of complications as may the ratio of the implant dose at the core vs. periphery.

Patterns and Predictors of Failure in Recurrent or Refractory Large B-Cell Lymphomas After Chimeric Antigen Receptor T-Cell Therapy

Chimeric antigen receptor T-cell (CAR T) therapy is capable of eliciting durable responses in patients with relapsed/refractory (R/R) lymphomas. However, most treated patients relapse. Patterns of failure after CAR T have not been previously characterized, and may provide insights into the mechanisms of resistance guiding future treatment strategies. This is a retrospective analysis of patients with R/R large B-cell lymphoma who were treated with anti-CD19 CAR T at a National Cancer Institute-designated Comprehensive Cancer Center between 2015 and 2019. Pre- and posttreatment positron emission/computed tomography scans were analyzed to assess the progression of existing (local failures) versus new, nonoverlapping lesions (de novo failures) and identify lesions at a high risk for progression. A total of 469 pretreatment lesions in 63 patients were identified. At a median follow-up of 12.6 months, 36 patients (57%) recurred. Most (n=31; 86%) had a component of local failure, and 13 patients (36%) exhibited strictly local failures. Even when progressing, 84% of recurrent patients continued to have a subset of pretreatment lesions maintain positron emission/computed tomography resolution. Lesions at a high risk for local failure included those with a diameter ≥5 cm (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.55-3.55; P < .001), maximum standardized uptake value ≥10 (OR, 2.08; 95% CI, 1.38-3.12; P < .001), or those that were extranodal (OR, 1.49; 95% CI, 1.10-2.04; P=.01). In the 69 patients eligible for survival analysis, those with any lesion ≥5 cm (n=46; 67%) experienced inferior progression-free survival (hazard ratio, 2.41; 95% CI, 1.15-5.04; P=.02) and overall survival (hazard ratio, 3.36; 95% CI, 1.17-9.96; P=.02). Most patients who recur after CAR T experience a component of local progression. Furthermore, lesions with high-risk features, particularly large size, were associated with inferior treatment efficacy and patient survival. Taken together, these observations suggest that lesion-specific resistance may contribute to CAR T treatment failure. Locally directed therapies to high-risk lesions, such as radiation therapy, may be a viable strategy to prevent CAR T failures in select patients.

Marginal Failures with Stereotactic Body Radiation Therapy(SBRT) for Early Stage Lung Cancer: Room for Improvement?

SBRT is an effective treatment for early stage non-small cell lung cancer (NSCLC). Prior series distinguish local from regional/distant recurrences, but detailed patterns of local failure are not well-described. We evaluate the location of local failures to provide further insight for treatment planning. Patients treated with SBRT for T1-2N0 NSCLC from 2007-2016 at a single institution were included. Prescribed dose was 48-54Gy in 3 to 5 fractions and planning target volume (PTV) margins were generally 5mm radially and 8mm superior/inferior. Site of first failure was classified as local, regional (hilar/mediastinal lymph nodes) or metastatic. For patients with a component of local failure, post-treatment diagnostic scans at time of recurrence were fused to the initial planning scan using rigid registration to lung features proximal to recurrence. The recurrence volume was delineated and compared to the treatment PTV. For each local failure, percent overlap of the PTV and recurrence volume was calculated. Distance from centroid (geometric center) of recurrence to PTV edge was measured in 3 planes and average distance was calculated. Local failures were categorized as: in-field failure (≥80% overlap or centroid >1cm inside PTV), marginal failure (20-80% overlap and centroid <1 cm inside/outside PTV), or involved lobe failure (overlap <20% or centroid >1cm outside PTV). Parametric statistics compared characteristics of recurrences. A total of 217 patients were treated with robotic radiosurgery (94%) or linac-based (6%) SBRT. 83% were T1 tumors, 69% upper lobe tumors, and 74% biopsy-proven malignancy. With a median follow-up of 20 months (range 0-98), 38% had progression of disease. 16% (N=34) had a component of local progression at time of first failure: 18 local only, 8 locoregional, 8 metastatic. 60% were pathologically confirmed. Of the local failures, 9 were classified as in-field, 15 marginal and 10 involved lobe. For in-field, marginal, and involved lobe failures there were differences in mean PTV/recurrence overlap (93% vs 43% vs 2%) and distance from centroid to PTV margin (1.39cm vs 0.56cm vs 1.78cm). For all local failures, PTV D95 was at least prescription dose. Marginal failures developed earlier than other local failures (mean 15 vs 25 months, p<0.05). Upper and lower lobe tumors had similar rates of local failure (16% vs 18%); however, 8 of the 11 local failures seen in lower lobe tumors were marginal failures compared to only 7 of 23 local failures in upper lobe tumors. Local progression is seen in roughly 16% of patients following SBRT. Marginal failures represent nearly half of these events, and appear to be of particular concern for lower lobe tumors. These findings highlight an opportunity to further evaluate margin size, motion management, and accuracy of dose calculations at the PTV margin to further improve local control in lung SBRT.

Carcinosarcoma: A single centre experience and population based study.

e22526 Background: Carcinosarcomas, consisting of biphasic morphological patterns including both epithelial and sarcomatoid components, are rare malignant tumours. We highlight the incidence and outcomes of this unique disease at our large cancer referral centre. Methods: A retrospective review consisting of carcinosarcoma patients over a 10 years span from 1/1/2005 to 1/1/2015 with follow up data through to 2/2017 to ensure at least 2 years of post-treatment data collection by purveying Electronic Medical Records, paper charts and where required, communication with peripheral facilities, was conducted. Inclusion and exclusion criteria were histologic confirmation and age &lt; 18 years respectively. A comprehensive literature review was also conducted to identify current outcomes trends. Results: Seventy patients meeting selection criteria were identified out of a total of 968 entries involving all soft tissue tumors. Incidence was mainly of gynecological origin (88.5%), in female patients (92.9%) and chiefly Grade 3 disease. Commonest presenting symptom was vaginal bleeding (54.3%). A majority received surgery (90.0%) primarily with a curative intent. 54.3% of the patients received chemotherapy and 51.4% received radiation; both largely in an adjuvant setting. Commonest treatment regimen was Carboplatin/Paclitaxel (73.7%) with a median of 6 cycles provided. Overall, 11 patients had a component of local failure with the latest failure recorded at 13.3 months. Conclusions: Treatment outcomes for carcinosarcoma over the years remain comparable to published results although there remains room for improvement. More research is required to identify strategies for improvement in both locoregional and systemic control. [Table: see text]

Angiosarcoma: A report of 67 patients and a review of the literature

Angiosarcomas (AS) are rare, aggressive tumors. Optimal treatment has not been well defined. The authors undertook a retrospective review of patients seen at their institution with the intent of identifying prognostic factors and optimal treatment strategies. Between 1955 and 1990, 67 patients with AS were seen at the University of California, at Los Angeles Medical Center. Follow-up ranged from 1 to 173 months with a median of 30 months. The overall prognosis was poor. The actuarial 2- and 5-year disease free survivals (DFS) were 44% and 24%, respectively. Of 52 recurrences after primary treatment, 81% (42 of 52) had a component of local failure. Twenty-eight patients had developed distant metastases at last follow-up. Of patients who received surgery (S) and radiation therapy (RT), with or without chemotherapy (CT), 5-year actuarial DFS was 43%, compared with 17% for patients who underwent S +/- CT as initial treatment (P = 0.03). Only 9% of patients (1 of 11) treated with RT +/- CT were rendered free of disease. Patients with AS usually present with high grade histology, and with multifocal disease. There is a propensity for both local recurrence and distant metastases. Our results and a review of the literature, suggest that S plus RT offers the best chance for long term control of this aggressive tumor. The role of CT remains undefined.

Angiosarcoma of the head and neck. The UCLA experience 1955 through 1990.

Between 1955 and 1990, 28 patients with angiosarcoma of the head and neck were seen at UCLA Medical Center, Los Angeles, Calif. Half the lesions arose on the scalp; the remainder occurred in the soft tissues of the face and neck. Nine patients presented with multifocal disease. Follow-up ranged from 3 to 159 months, with a median of 32 months. The overall prognosis was poor, with a 5-year disease-free survival of 26% (7/27 patients). Of 21 patients having recurrences after primary treatment, 90% (19/21 patients) had a component of local failure. Distant metastasis had developed in nine patients at last follow-up. Of patients treated initially with surgery alone, 8% (1/12 patients) remain disease free vs 67% (4/6 patients) who received postoperative radiation therapy, with or without chemotherapy. Only one (14%) of seven patients treated primarily with radiation therapy with or without chemotherapy was rendered disease free. Angiosarcoma usually presents with high-grade histologic features and frequently with multifocal disease. There is propensity for both local recurrence and distant metastasis. Our results and a review of the literature suggest that combined modality therapy offers the best chance for long-term control in patients with angiosarcoma of the head and neck.

Endometrial cancer with para-aortic adenopathy: Patterns of failure and opportunities for cure

Purpose:To examine the outcome of patients with advanced endometrial cancer whose para-aortic involvement was diagnosed pathologically or lymphographically. Methods and Materials. Fifty patients from four institutions were treated between 1959 and 1990 with preoperative, post-operative, and primary radiotherapy. Para-aortic disease was diagnosed pathologically in 26 patients and lymphographically in the remaining 24 patients. Pathologically diagnosed patients underwent debulking of grossly involved nodes. All patients received external beam treatment through pelvic and para-aortic portals. Median prescribed dose to the pelvic and para-aortic fields was 50 and 47 Gy, respectively. Those treated with primary or pre-operative irradiation also received intrauterine brachytherapy. Results: The actuarial 5-year disease-free survival was 46% for all patients. Para-aortic failure was significantly decreased among patients undergoing lymph node resection (13% versus 39%, respectively). Relapse-free survival and pelvic control tended to improve among patients receiving surgery plus irradiation in comparison to those treated by irradiation alone. Distant metastases were most common among patients with high grade lesions. Conclusions: Long-term disease-free survival is achievable in endometrial cancer patients with para-aortic lymphadenopathy who are treated with extended-field radiotherapy. Cure is most attainable among patients with well differentiated, early clinical stage disease who receive combined modality treatment. Survival and local failure are similar for radiologically and pathologically diagnosed patients; however, para-aortic failure as a component of local failure was increased in patients who did not undergo surgical debulking of the adenopathy.

Further experience with radiation therapy and concomitant intravenous chemotherapy in advanced carcinoma of the lower female genital tract

Sixty-seven patients with advanced carcinoma of the lower female genital tract (cervix, vagina, and vulva) were treated with radiation and concomitant intravenous cisplatin and/or 5-fluorouracil. Fifty-seven patients (85%) responded completely clinically. Thirty-five (61%) complete responders recurred with a median time to recurrence of 6 months. Twenty-six of the thirtyfive patients who recurred had some component of local failure. The 22 complete responders who have not recurred have been followed a median of 13 months. Acute toxicity was minimal, with only 6 patients requiring interruption of therapy. Nine (13%) patients developed severe late complications and eight required surgery. The actuarial 5-year survival is 22%. This treatment regimen is disappointing in terms of both survival and local control.

Long-term results of infusional 5-FU, mitomycin-C, and radiation as primary management of esophageal carcinoma

An analysis of the results of 90 patients with esophageal cancer treated prospectively with combined chemotherapy and radiation without surgery and with a median follow-up of 45 months is presented. Fifty-seven patients with Stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m 2/24 hr) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m 2) was administered as a bolus injection on day 2. Thirty-three patients received palliative treatment (5,000 cGy plus above chemotherapy) for Stage III, IV, or otherwise advanced disease (extraesophageal spread, distant metastases, multiple primary tumors). Follow-up ranged from 1 month to 96 months. Overall median survival of Stage I and II patients was 18 months with 3- and 5-year actuarial survival of 29% and 18%, respectively, while the median disease specific survival was 20 months with an actuarial disease specific survival of 41% and 30% at 3 and 5 years, respectively. A multivariate analysis of sex, histology, tumor location, and tumor size on survival revealed that the effect of stage was highly significant (Stage I versus 11, 73% versus 33% at 3 years, p = .01), whereas the effect of sex approached significance (females versus males, 57% versus 34% at 3 years, p = <.1). The actuarially determined local relapse-free rate for Stage I and II patients at both 3 and 5 years was 70%. Multivariate analysis again indicated stage to be highly significant (Stage I versus 11,100% versus 60% at 3 years, p = <.01), whereas sex approached significance (female versus male, 75% versus 66% at 3 years, p = .07). The pattern of failure may be altered with this treatment regimen from local failure to one dominated by distant metastases. Of 29 patients who have failed, 14 (48%) had any component of local failure, whereas 21 (72%) had a distant failure as a component of failure. The median survival of patients with Stage III or IV disease was 9 months and 7 months, respectively. Palliation in this group of patients with advanced disease was good as 77% were rendered free of dysphagia post-treatment, and 60% were without dysphagia until death with a median dysphagia-free duration of 5 months. Severe toxicities were uncommon and nearly all were transient. Eleven of 90 patients (12.2%) had severe acute toxicities, whereas only 3 patients (33%) developed significant late treatment-related complications requiring hospitalization for management.

Patterns of failure in patients with stage I, grade 3 carcinoma of the endometrium

Patients with high grade, early stage endometrial carcinoma are reported to have worse survival and local control rates than those with low grade carcinomas. To define failure patterns further in patients with FIGO Stage I, grade 3 endometrial carcinomas, the patients from three institutions who received adjuvant or definitive radiation (RT) were analyzed. Of 119 patients meeting the criteria of Stage I, grade 3 endometrial carcinoma, 57 patients received preoperative radiation, 49 patients received postoperative radiation, and 10 patients received definitive radiation with 5-year actuarial survival rates of 64%, 73%, and 65%, respectively. Three additional patients received both preoperative and postoperative treatment. The overall local control rate was 88% with a median follow-up of 70 months. Of 36 patients who failed, 14 had a component of local failure, and 31 had a component of distant failure. Eighteen of 31 distant failures involved metastatic spread to the abdominal cavity. Recurrence patterns by method of treatment are documented. Patients with high grade tumors do have a propensity for distant metastasis. Clinical investigation into the value of systemic therapy is necessary.

Patterns of failure after curative resection of pancreatic carcinoma

Thirty-six patients underwent curative resection of a primary pancreatic carcinoma from January 1977 to September 1987; 26 had Whipple resections, seven had total pancreatectomies, and three had distal pancreatectomies. Twenty-six patients manifested recurrent disease, four died of intercurrent disease, and six were apparently cured. Median survival was 11.5 months with actuarial survival at 2 and 5 years of 32% and 17%, respectively. Of the eventual recurrences, 19% were local only (pancreatic bed, regional nodes, adjacent organs, and immediately adjacent peritoneum) and 73% had a component of local failure. All patients failing did so with a component in the intraabdominal cavity. Peritoneal (42%) and hepatic failures (62%) were common. Extraabdominal metastases were documented in only 27%, but never as a sole site. Fourteen patient and tumor characteristics were evaluated for any relationships with failure or survival. No single variable independently predicted for local failure. However, a group of three (age greater than 60 years, T2 or T3 stage, and location of tumor in the body or tail) was associated with a substantial local failure risk (85% of all patients with local failure). Multivariate analysis showed that low tumor grade (P = 0.002), female sex (P = 0.002), and adjuvant radiation (P = 0.02) were all independent predictors of prolonged survival. Ten patients were treated in an adjacent setting. Those given 55 Gy or greater had improved local control (50% versus 25%) and cure (33% versus none) when compared with patients treated to lower doses. The authors conclude that local failure after curative resection remains a significant problem and further efforts to improve local control are warranted. However, peritoneal and hepatic relapses occur frequently. Thus, adjuvant treatment strategies using wide-field radiation techniques or intraperitoneal therapy, in combination with local tumor bed irradiation and chemotherapy, should be explored.

Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma

Management of early endometrial carcinoma often consists of surgicopathologic staging followed by adjuvant radiation therapy (RT) for patients at risk of local recurrence. While an intracavitary vaginal cuff boost (VCB) is commonly given after external beam radiation therapy, its effects on local control and complication rates are unknown. To assess these effects, we reviewed 157 patients with FIGO Stage I (n = 134) or incidentally diagnosed (n = 23) endometrial adenocarcinomas. After surgery and external radiation therapy, 103 patients (65.6%) received a vaginal cuff boost of 3000–5000 cGy surface dose (Group I) and 54 (34.4%) did not (Group II). One hundred and two Group I and 52 Group II patients were evaluable for analysis. Median follow-up was 78.0 months for Group I and 60.0 months for Group II. Despite a preponderance of poor prognostic factors in Group II, no significant difference in local failure was seen. A component of local failure was seen in 6 Group I patients (6.0%) and 4 Group II patients (7.7%), p = 0.74. Distant failure, reflecting more advanced disease, was higher in Group II (19.2%) than in Group I(9.0%). Late complications included rectal bleeding/proctitis in 18.6% of Group I patients and 3.8% of Group II patients ( p = 0.01). Overall, grade 2 complications occurred in 27.5% and 15.4% of Group I and II patients, respectively ( p = 0.09). No difference in frequency of grade 3 complications was evident. Based on this retrospective study, intracavitary vaginal cuff boost after surgery and postoperative external beam radiation therapy does not appear to improve local control in early endometrial adenocarcinoma. Its possible effect on complication rates is uncertain.

Postoperative local abdominal irradiation for cancer of the colon above the peritoneal reflection.

A retrospective analysis of 82 patients with cancer of the colon above the peritoneal reflection who received postoperative local abdominal irradiation was undertaken to assess the survival, patterns of failure, and toxicity of treatment. Forty-eight patients (adjuvant group) had a complete resection, but were felt to be at high risk for local relapse and received postoperative local abdominal irradiation. Thirty-four patients had gross residual disease following surgery. The 5-year actuarial survival and local relapse free survival were 67 and 67%, respectively, in the adjuvant group. In this group, local relapse was observed in 9 of 28 patients with Stage C disease in contrast to 3 of 20 patients with Stage B2 disease; 1 of 14 patients with lesions in the right colon failed locally compared to 11 of 35 patients with lesions in the left. Only 2 of the 34 patients with gross residual disease remained relapse free from 93% of patients having a component of local failure. The majority of the treatment morbidity was seen in patients with gross residual disease. Prospective randomized studies should be done to determine the efficacy of postoperative irradiation in patients with colon carcinoma who are at high risk for local recurrence following surgical resection.