Actuarial Relapse-free Survival Research Articles

TARGIT E(lderly): Prospective phase II trial of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer.

563 Background: TARGIT E is a prospective, multicentric single-arm phase II trial (NCT01299987; Neumaier et al. BMC Cancer 2012) that is based on the experimental arm of the protocol of the international randomized TARGIT A study. The trial was designed to investigate the efficiency of a risk-adapted approach consisting of a single dose of intraoperative radiotherapy (IORT) followed by whole breast radiotherapy (WBRT) only when risk factors are present in elderly patients. Methods: Patients with low-risk breast cancer (≥70 years, cT1, cN0, cM0, invasive carcinoma of no special type) were enrolled between February 2011 and September 2014. During breast conserving surgery, a single dose of 20 Gy of low-energy IORT was given (Intrabeam, Carl Zeiss Meditec, Germany). Additional postoperative WBRT (46 – 50 Gy) was applied in case risk factors (larger size, other histology, free margin < 1 cm, lymphatic vessel invasion (L1), positive nodes, multifocality/multicentricity, extensive intraductal component (EIC)) were present. Systemic therapy was applied according to international standards and guidelines. The primary outcome was the local relapse rate. Discontinuation of the trial was judged to be necessary if the local relapse rates exceed 3/4/6% at 2.5/5/7.5 years. Results: A total of 541 patients were screened. Of those 474 patients were enrolled, whereas 347 (73.1%) received IORT only, 99 (10.8%) IORT plus WBRT, 22 (4.6 %) WBRT only and 7 (1.5%) surgery only with no subsequent adjuvant therapies. After a median follow-up of 3.25 years, four ipsilateral in-breast recurrences were observed (after 11, 33, 42 and 43 months) resulting in an actuarial local relapse-free survival of 99.8% after 2.5 years and 98.5% after 5 years. Conclusions: The results of the prospective TARGIT E trial consolidate earlier reports from the randomized TARGIT A trial, supporting the use of accelerated partial breast radiotherapy (APBI) in selected patients. The observed local relapse rates at 2.5 and 5 years are far below the predefined stopping rules. Clinical trial information: NCT01299987.

Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery

Neoadjuvant chemotherapy is being actively tested as an emerging alternative for the treatment of locally advanced colon cancer (LACC) patients, resembling its use in other gastrointestinal tumors. This study assesses the mid-term oncologic outcome of LACC patients treated with oxaliplatin and fluoropyrimidines-based preoperative chemotherapy followed by surgery. Patients with radiologically resectable LACC treated with neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed. Radiological, metabolic, and pathological tumor response was assessed. Both postoperative complications, relapse-free survival (RFS), and overall survival (OS) were studied. Sixty-five LACC patients who received treatment were included. Planned treatment was completed by 93.8% of patients. All patients underwent surgery without delay. The median time between the start of chemotherapy and surgery was 71days (65-82). No progressive disease was observed during preoperative treatment. A statistically significant tumor volume reduction of 62.5% was achieved by CT scan (39.8-79.8) (p<0.001). It was also observed a median reduction of 40.5% (24.2-63.7%) (p<0.005) of SUVmax (Standard Uptake Value) by PET-CT scan. Complete pathologic response was achieved in 4.6% of patients. Postoperative complications were observed in 15.4% of patients, with no cases of mortality. After a median follow-up of 40.1months, (p 25-p 75: 27.3-57.8) 3-5year actuarial RFS was 88.9-85.6%, respectively. Five-year actuarial OS was 95.3%. Preoperative chemotherapy in LACC patients is safe and able to induce major tumor regression. Survival times are encouraging, and further research seems warranted.

Testicular seminoma clinical stage 1: treatment outcome on a routine care level

PurposeClinical stage 1 (CS1) testicular seminoma involves an almost 100 % disease-specific survival in controlled clinical trials. We aimed to find out whether these results can be matched in patients managed on the routine care level.Patients, methodsIn total, 725 patients with seminoma CS1 were prospectively enrolled from 130 institutions. Adjuvant management as decided by local physicians involved surveillance (n = 256), radiotherapy (41), 1× Carboplatin (362), and 2× Carboplatin (66). We registered type of management, age, duration of follow-up (F/U), relapse, rete testis invasion (RTI), and tumor size. Actuarial relapse-free survival curves were calculated for treatment modalities and stratified for tumor sizes and RTI. A Cox regression model was calculated to explore for factors influencing relapses.ResultsDisease-specific survival was 100 %. Crude relapse rates were 8.2, 2.4, 5.0, and 1.5 % for surveillance, radiotherapy, 1× Carboplatin, and 2× Carboplatin after a median F/U of 30 months. RTI and tumor size were not associated with progression in surveillance patients. One course Carboplatin caused relapses in 6.8 % in tumor sizes >4 cm and 9.3 % (actuarial 13 %) in sizes >5 cm. The Cox model revealed the association of tumor size with recurrence in the entire seminoma population (Hazard ratio 1.17; 95 % confidence intervals 1.03–1.33).ConclusionsThe overall outcome of CS1 seminoma managed on the routine care level mirrors that of controlled trials. Unexpectedly, the risk factors in surveillance patients were not confirmed, but tumor size proved to be a risk indicator in the entire group of seminoma. Importantly, one course Carboplatin involved low efficacy to control the disease in large tumors.Electronic supplementary materialThe online version of this article (doi:10.1007/s00432-016-2162-z) contains supplementary material, which is available to authorized users.

Pelvic Lymph Nodes Displacement in High-Risk Prostate Cancer Patients Treated With Image-Guided IMRT With 2 Independent Target Volumes

Purpose/Objective(s): To report initial experience of biochemical outcomes and the acute and late toxicity in 200 patients with clinically localized prostate cancer treated with volumetric modulated arc therapy (VMAT). Materials/Methods: Between November 2007 and September 2011, 200 patients with clinically localized prostate cancer were treated with VMAT using daily cone-beam computed tomography acqusition. Treatment planning systems used were avoidance conformal-based in 77 patients and multileaf collimator-based in 123 patients. All plans were generated on an inverse-planning approach. A total of 182 patients (91%) were treated to 76 Gy, and 18 patients (9%) were treated to Z < 72 Gy. Acute and late toxicities were scored according to CTCAE grading scales. PSA relapse was defined according to Phoenix definition. The mean follow-up time was 50 months (range: 7-85 months). Results: Two patients (1%) developed acute Grade 2 or worse GI toxicity. Thirty-nine patients (19%) developed acute Grade 2 GU symptoms, and no one experienced Grade 3 GU toxicity. Six patients (3%) developed late Grade 2 rectal bleeding. Two patients (1%) experienced Grade 3 rectal toxicity requiring either one or more transfusions or a laser cauterization procedure. No Grade 4 rectal complications have been observed. The 5year actuarial likelihood of late Grade 2 or higher rectal bleeding was 3.4%. Twenty patients (10%) experienced late Grade 2 GU toxicity, and no one developed Grade 3 GU toxicity. The 5-year actuarial likelihood of late Grade 2 or higher GU toxicity was 11.6%. The 5-year actuarial PSA relapse-free survival rates for low-, intermediate-, and high-risk group patients stratified according to NCCN criteria, were 100%, 91,8%, and 85.3%, respectively. Conclusions: Our initial data demonstrate the feasibility of VMAT in patients with localized prostate cancer. Acute and late rectal toxicities seem to be dramatically reduced compared with what has been observed with conventional radiation therapy techniques. Short-term PSA control rates were excellent. Based on our promising initial experiences, VMAT is an established novel conformal radiation delivery method for localized prostate cancer at our institution. Further studies in a larger population are required to determine long-term results in VMAT. Author Disclosure: K. Shiraishi: None. K. Yamamoto: None. A. Haga: None. A. Sakumi: None. K. Nakagawa: None.

Early Infusion Of Donor-Derived CIK Cells As Consolidative Immunotherapy Following Non-Myeloablative Allogeneic Transplantation: Safety and Feasibility

Allogeneic hematopoietic cell transplantation (allo HCT) is the only curative option for patients with Myelodysplastic syndromes (MDS). MDS is primarily a disease of older patients for whom ablative allo HCT is often not feasible. We have treated patients greater than 50 years with high risk MDS with a non-myeloablative conditioning regimen of total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (ATG) and have found very low incidences of acute graft versus host disease (GVHD) and non-relapse mortality (NRM). Relapse remains the main cause of treatment failure. We initiated a combined phase I/II trial of prophylactic post-transplantation infusion of donor-derived Cytokine Induced Killer (CIK) cells as consolidative therapy after TLI-ATG conditioning for patients with MDS. CIK cells are ex vivo expanded CD3+CD8+NKG2D+ cells that are cytotoxic to multiple cancers in vitro yet appear not to cause GVHD. A previous Phase I/II trial of CIK infusions for patients with relapsed malignancy after allogeneic HCT demonstrated that matched-related donor derived CIK cells, at a dose of 1x108 CD3+ cells/kg was well tolerated1. The MTD of unrelated donor derived CIK cells was unknown. Four patients were treated on a Phase I dose escalation trial of unrelated donor derived CIK cells. Expansion of unrelated donor cells was feasible and there were no infusional toxicities or adverse events at any CIK dose tested. Fourteen patients, including 9 with unrelated donors, were treated on a Phase II trial of prophylactic CIK infusion with a goal dose of 1 x 108 CD3+ cells/kg. The median age was 60 years (range 54-69). Three patients had prior evolution to AML. Two patients did not receive CIK cells because the CD34+ cell dose from unrelated donors did not meet the pre-specified threshold for culture inoculation. One patient did not receive CIK cells because of active uncontrolled infection at the time of scheduled CIK cell infusion. The remaining 11 patients received the target dose of 1x10^8 CD3+cells/kg between days 21 and 35 post PBSC infusion. The median CD3+ and CD3+ CD8+ NKG2D+ cell content of the bulk cultures was 96% (range 70-99%) and 63 (13.6-81%), respectively. The median follow up time of living patients is 264 days. There were no infusional toxicities and no patient experienced acute GVHD grades II-IV. There has been no NRM. Of the 11 patients treated on the Phase II trial and that received CIK cells, 3 patients relapsed (at days 74, 147, and 174) and two patients with relapse died. Two year actuarial relapse free survival (RFS) and overall survival (OS) was 62% and 71%, respectively, which compares favorably to our experience without allo CIK after TLI-ATG (2-year RFS 38% and OS 41%). All three of the patients that did not receive CIK cells died; two of relapse, and one of GVHD at day 195. Therefore, by intention-to-treat analysis of all 14 patients, the 2-year actuarial RFS and OS was 52% and 65%. In summary, allo CIK cells administered early in the post-transplant period appear to be safe without increasing the risk of acute GVHD. Further, the infusion of allo CIK cells may improve outcome although additional patients and further follow-up are needed. 1Laport GG, Sheehan K, Baker J, et al. Adoptive immunotherapy with cytokine-induced killer cells for patients with relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2011;17(11):1679-1687. Disclosures:Off Label Use: Off label use of Thymoglobulin (ATG).

A case of lung metastasis in myxoinflammatory fibroblastic sarcoma: analytical review of one hundred and thirty eight cases

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue tumour first identified at the end of the 1990s. This study presents our experience and literature reviews focusing on risk of recurrence. Rizzoli Orthopaedic Institute database and literature were searched for patients with MIFS observed from 1997 to 2012. Data were analysed in a new database. Five patients underwent surgery at our institute, and 133 cases were retrieved from the literature. Not all clinicopathological data were available: 76/138 were men (55%), median age was 45 [interquartile range (IQR) 34-56] years, median tumour size was three (IQR two to five) centimetres. Common sites of occurrence were hand (24%), fingers (23%) and foot (20%). Pain was present at diagnosis in 14/82 patients (17%), with a median duration of seven (IQR three to 12) months. Surgery was performed for a suspected benign tumour in 88 patients (74%). Resection was incomplete in 45/71 cases (63%); re-excision was performed in 32/45 (71%). At a median follow-up of 26 months, 26/118 patients (22%) developed recurrent disease; median time to recurrence was 15 months (IQR seven to 26). Actuarial relapse-free survival (RFS) at one, three and five years was 93%, 72% and 67%, respectively. At univariate analysis, only symptom duration of six months or less was significantly associated with a worse RFS (p = 0.046). Metastatic disease to lymph nodes and/or lungs was observed in four patients (3%). Clinicopathological findings confirm the low-grade nature of MIFS. However, local recurrence occurs, and patients may be affected by aggressive forms with a potential for distant metastases. Follow-up is strongly advised.

A 10-year Single Institutional Experience Using Adjuvant External Beam Radiation Therapy for Extremity Soft-tissue Sarcomas

A 10-year Single Institutional Experience Using Adjuvant External Beam Radiation Therapy for Extremity Soft-tissue Sarcomas

REDUCING A POSTOPERATIVE RADIATION DOSE IN THE COMBINED-MODALITY TREATMENT OF LOCALLY ADVANCED BREAST CANCER

The purpose of the study was to evaluate the efficiency of traditional versus low-dose postmastectomy chest radiation according to local control criteria, overall and relapse-free survival rates, and the frequency of postradiation cardiac complications. The efficiency of treatment was compared in two groups of patients with Stages II-IIIB breast cancer: 1) 129 patients who received normal-dose (50 Gy in 25 fractions applied to the chest) radiotherapy (RT) and 2) 82 patients who had low-dose (40 Gy in 20 fractions applied to the chest) RT. The latter followed Madden mastectomy in all cases. In all the patients, regional areas were irradiated with standard doses of 46-50 Gy concurrently with chest radiation. The frequency and quality of neoadjuvant and adjuvant chemotherapy were similar in the groups. The median follow-up was 111 and 95 months in each group, respectively. In the normal- and low-dose RT groups, 5-year actuarial local-regional progression rates were 6.2±2.1 and 3.7±2.1%, respectively (p = 0.4). In Groups 1 and 2, late metastases were detected in 34.6±4.2 and 19.5±4.4%, respectively (p &lt; 0.05). Five-year actuarial relapse-free survival was 71.5±6.4% in the low-dose RT group and 53.5±5.4% in the normal-dose RT one, respectively (p = 0.07). Five-year overall survival was 65.3±5.6 and 72.2±6.3%, respectively (p = 0.08). The patients with a left-sided tumor process were noted to have late ECG cardiac changes in 55±11.1% of cases in the low-dose RT group and in 75±9.7% in the normal-dose RT one (p &gt; 0.05). The findings suggest that there are no statistically significant differences in the rates of local-regional progression, overall and relapse-free survival in the normal- and low-dose RT groups. The proposed procedure for reduced postmastectomy chest radiation in combination with current chemotherapy regimens can reduce the risk of cardiac toxicity, without decreasing the therapeutic effectiveness characteristic of the traditional procedure.

Treatment of ductal carcinoma in situ (DCIS) with lumpectomy and accelerated whole breast radiation therapy with concomitant boost (ARTB).

93 Background: The efficacy of accelerated radiation therapy (RT) for treating early stage invasive breast cancer has been established (Whelan T et al: NEJM, February 2010). But the role of accelerated schedules in treating patients with DCIS still needs to be defined. We have previously described the feasibility and low toxicity when using ARTB after lumpectomy (Chadha M et al: Int J Radiat Oncol Biol Phys 2007; 69). The objective of this study is to evaluate early outcomes in patients with DCIS treated with lumpectomy and ARTB, and to compare local recurrence rates of ARTB and conventional fraction (fr) RT with sequential boost (CRT). Methods: This study includes patients diagnosed to have primary DCIS treated with lumpectomy and RT. Patients with DCIS who had history of contralateral synchronous or metachronous invasive cancer were excluded. We identified 215 patients from our breast cancer database as having met this selection criteria; 54 patients received ARTB on an IRB approved protocol, and 161 patients matched by prognostic factors constituted the comparative CRT group. ARTB delivered 40.5Gy in 15fr to the breast, and with concomitant boost 45Gy in15fr was delivered to the lumpectomy boost volume. CRT delivered 46.8Gy in 26fr with sequential boost of 14Gy in 7fr. The patients were well matched with no significant difference in the distribution of known prognostic factors including age, nuclear grade, margin status, receptor status, and Body Mass Index between the groups. Results: The overall median follow up was 3.5 years (0.5 years–11.4 years). Actuarial 5-year local relapse-free survival was 95%. The actuarial 3-year local relapse rate was 2% and 0% for CRT and ARTB groups, respectively (p = 0.22). Local recurrence was observed in 9 patients with a median time to failure of 4.3 years (0.5 years to 8.6 years); 4/9 had grade 3 DCIS; 1 patient with grade 3 had close final margin (&lt;1 mm); 5/9 patients received hormone therapy. Conclusions: With the follow up to date, we observed excellent outcomes in patients with DCIS treated by lumpectomy and RT. These preliminary results suggest comparable local control between ARTB and CRT. Additional studies and longer follow-up are needed.

Retroperitoneal Histologic Findings of Patients With Elevated Serum Alpha-fetoprotein and Pure Seminoma at Orchiectomy

To report the retroperitoneal histologic findings from a contemporary series of patients with pure seminoma at orchiectomy with an elevated serum α-fetoprotein (AFP) level. These patients underwent treatment on the assumption that the lesion was nonseminomatous germ cell tumor (NSGCT). We identified 22 patients from 1989 to 2009 with pure seminoma diagnosed at orchiectomy with an elevated serum AFP level (>15 ng/mL) either before or after orchiectomy. The retroperitoneal histologic and relapse data are reported. The median preorchiectomy and prechemotherapy serum AFP level was 248 ng/mL (interquartile range 48-4693) and 279 ng/mL (interquartile range 66-5311), respectively. The percentage of patients with clinical Stage I, II, and III disease was 5%, 50%, and 45%, respectively. The percentage of patients with a good, intermediate, and poor risk status according to the International Germ Cell Cancer Collaborative Group was 32%, 32%, and 36%, respectively. Of the 22 patients, 21 underwent induction chemotherapy followed by retroperitoneal lymph node dissection. Overall, 67% of patients had NSGCT elements in the retroperitoneum. The histologic findings were pure teratoma in 38%, malignant transformation in 14%, and viable NSGCT in 14%. Also, 59% had some component of teratoma in the retroperitoneum. Only 1 patient (5%) had any seminoma in the retroperitoneum, but this patient also had retroperitoneal teratoma. Of the 22 patients, 7 developed a relapse and received salvage chemotherapy. The actuarial relapse-free survival rate at 5 and 10 years was 76% and 61%, respectively, reflecting the high percentage of patients with Stage II-III disease. Pure seminoma at orchiectomy with an elevated serum AFP level portends a high likelihood of NSGCT elements in the retroperitoneum.

Locoregional Recurrence in Patients with Triple-negative Breast Cancer: The Impact of Radiotherapy

Results:Inthe analyzedcohortof 52patients,37 (71%)receivedradiation therapyas part of their treatmentregimen, and 15(29%) receivednoradiotherapy.Regardingdemographics,themedianagewas50years(range:31-79y);52%ofpatientswerewhite,44% were black; 58% were smokers; and 27% had a family history of breast cancer. The median follow-up in months from the completion of treatment is 19.7 (range: 2.0-48.0). For the entire group, overall 1-, 2- 3- and 4- year survivals (OS) from the completion of the treatment are 92%, 87%, 87%, and 58%, respectively. Of the patients who received radiation therapy, 25 (68%) did so in the setting of breast conservation. Patients who received radiation therapy were significantly more likely to be of a higher T-stage (p\0.001) and N-stage (p\0.001) than patients who did not receive radiotherapy. The 4-year actuarial locoregional relapse-free survival (LRFS) probability for patients who received radiation is much higher than those who did not receive radiation (66.1% vs. 29.5%, p = 0.016). Conclusions: Despite their significantly lower T- and N-stage, patients with triple-negative breast cancer who do not undergo radiation therapy have a significantly higher locoregional recurrence. Triple-negative status should be considered a factor in offering postmastectomy radiotherapy. This study is limited due to its small sample size and these findings should be confirmed by a larger, multi-institutional study.

Dose escalation by high-dose 3D-conformal radiotherapy (HD-3D-CRT) or low-dose 3D-conformal radiotherapy plus HDR brachytherapy (LD-3D-CRT+HDR-B) for intermediate- or high-risk prostate cancer: Early results of a prospective comparative trial

5118 Background: To report early and late toxicity and preliminary biochemical outcome in 445 patients with intermediate- or high-risk clinically localized prostate cancer treated with either HD-3D-CRT or with LD-3D-CRT+HDR-B. Methods: Between December 1999 and October 2005, 445 patients (pts) with PSA'10, Gleason score'6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were assigned to one of the two treatment groups: 76 Gy HD-3D-CRT to the prostate in 38 fractions (group 1; 223 patients) or 46 Gy LD-3D-CRT+ 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 222 patients). Both groups were well balanced taking into account patient's as well as tumors’ characteristics. Toxicities were scored by the EORTC /RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. Results: All pts completed treatment. None pts included in the group 1 or 2 experienced grade 3 rectal toxicity. 28 pts of group 1 (12.5%) and 6 pts of group 2 (2.7%) developed grade 2 rectal toxicity (rectal bleeding or urgency). 15 pts in group 1 (6.7%) and 3 pts in group 2 (1.3%) developed grade 1 rectal bleeding (less than 2 times/week). In group 1 and 2, 81.8%and 95,9% of pts were free from rectal reactions respectively (p &lt; 0.005). 19 pts in each group developed acute Grade 2 urinary symptoms (mainly dysuria), and none experienced urinary retention. No pts (0%) developed Grade 3 or 4 rectal or urinary complications. With a mean follow-up of 55 months, the 5-year actuarial PSA relapse-free survival rates for intermediate- and high-risk group 1 pts were 92 and 91 % respectively and 97 and 96 % for group 2 pts (p &lt; 0.06). Conclusions: High-dose 3D-EBRT +HDR brachytherapy is a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute and late rectal and urinary complications were significantly reduced with the combined treatment, compared with what was observed with high-dose conventional, 3D-CRT. Short-term PSA control rates tends to be better with in the HDR-boosted patients as spected by higher effective-dose. No significant financial relationships to disclose.

Prognostic significance of anatomic subsites: Results of radiation therapy for 66 patients with localized orbital marginal zone B cell lymphoma

Background and purpose To evaluate the prognostic significance of anatomic subsites for marginal zone B cell lymphoma confined to the orbit. Materials and methods From 1995 to 2005, 66 patients (80 lesions) with marginal zone B cell lymphoma, confined to the orbit, received radiation therapy at Samsung Medical Center. The most frequent site of involvement was conjunctiva (29 patients) followed by retrobulbar (20 patients), eyelid (10 patients) and lacrimal gland (7 patients). The median follow-up duration was 50 (13–114) months. Results Local relapse developed in two patients, systemic relapse in three, and metachronous relapse in two. The 5-year relapse-free survival rate was 92.0%. A primary tumor located at lacrimal gland was the only poor prognostic factor for relapse ( p = 0.023, HR = 12.263, 95% CI = 1.360–110.602). The 5-year actuarial relapse-free survival rate was 57.1% for lacrimal tumor versus 95.8% for non-lacrimal tumors ( p = 0.002). Conclusions Localized primary orbital MALT lymphomas respond extremely well to moderate-dose RT, with a high local control rate and durable disease free status. However, primary lacrimal involvement maybe related to future relapse more frequently than other orbital subsites.

Impact of Time Duration After Neoadjuvant Therapy to Surgery on Response and Outcome in Rectal Cancer Patients

Until the 1970s and 1980s, surgery was often the only therapy used in the treatment of patients with rectal cancer. However, analyses of patterns of failure demonstrated that pelvic recurrence after surgery was common, resulting in significant patient morbidity and death. To reduce these high failure rates, cooperative group studies from the USA evaluated different strategies of postoperative radiation therapy and 5-fluorouracil (5-FU)-based chemotherapy. These study results showed that adjuvant radiation therapy and chemotherapy improved local control and survival versus surgery alone, leading to the routine integration of these modalities into daily practice in the USA. To address the potential merits of preversus postoperative therapy, neoadjuvant trials have been pursued in rectal cancer patients. The CAO/ARO/ AIO-94 trial from Germany directly compared preto postoperative approaches. This landmark study demonstrated that by simply altering the sequence of radiation therapy and chemotherapy with respect to surgery, there were improved rates of compliance, local control, sphincter preservation, and reduction in acute and late toxicities with preoperative radiation therapy and chemotherapy. In the preoperative therapy arm, patients received 50.4 Gy in 28 fractions over 5.5 weeks with concurrent 5-FU, followed by surgery 6 weeks later. Significant tumor downstaging was observed after preoperative combined modality treatment, leading to an 8% complete pathologic response rate. These findings led to a new standard of care for the treatment of rectal cancer in the USA. Modifications of this neoadjuvant approach have been investigated in an effort to increase the percentage of responders. Recent European trials have further evaluated the role of concurrent 5-FU-based chemotherapy with radiation therapy in the neoadjuvant treatment of rectal cancer. Trial results from the European Organization for Research and Treatment of Cancer (EORTC), Federation Francophone de la Cancerologie Digestive (FFCD), and Poland indicated improved complete pathologic response rates of 11.7–16% and local control for patients treated with concurrent 5-FU and radiation therapy versus radiation therapy alone. In these trials, patients received 45–50.4 Gy in 25–28 fractions over 5–6 weeks with concurrent 5-FU-based chemotherapy, followed by surgery performed 3–10 weeks after completion of neoadjuvant therapy. Other studies have shown the impact of radiation dose escalation on the rate of pathological complete response to neoadjuvant therapy. In a review of 134 patients at Princess Margaret Hospital who received 40, 46 or 50 Gy in 2-Gy fractions with continuous-infusion 5-FU, the pathological complete response was 18%, 23%, and 33% for the three dose levels, respectively. The 2-year actuarial local relapse-free survival was 72%, 90%, and 89%; disease-free survival was 62%, 84%, and 78% and overall survival was 72%, 94%, and 92% for the 40, 46, and 50 Gy levels, respectively. Patients receiving doses of 46 or 50 Gy had improved outcomes compared with patients receiving 40 Gy, but there was no significant difference between 46 or 50 Gy. In contemporary therapy, patients routinely receive 50 Gy of external beam irradiation with chemotherapy. Improved disease-free and overall survival rates have been observed with the addition of newer chemotherapeutic agents (oxaliplatin, irinotecan) to Published online July 29, 2008. Address correspondence and reprint requests to: Christopher G. Willett, MD; E-mail: christopher.willett@duke.edu

Combined treatment image guided-intensity modulated radiotherapy (IG-IMRT) plus high-dose rate brachytherapy (HDR) and hormonotherapy (HT) as treatment for high-risk prostate cancer: Five-year result of a phase II study

15571 Background: To report early and late toxicity and preliminary biochemical outcome in 345 patients with high-risk (Gleason &gt;=7; PSA&gt;20 or T2c-T3) clinically localized prostate cancer treated with combined high-dose-rate brachytherapy and IMRT (IMRT-HDR) to the prostate and seminal vesicles with 24–36 months of hormononal treatment (goserelin+bicalutamide) (HT). Methods: Between 12/1999 and 10/2003, 345 patients with PSA&gt;20, Gleason score&gt;6 and/or T2c-T3 N0 M0 prostate cancer were treated with IG-IMRT followed by HDR implant to the prostate and HT. Patients were randomly assigned to receive HT for 24 (group 1, 172 patients) or 36 months (group 2, 173 patients). Acute and late toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. PSA failure was defined as nadir +2.0 ng/ml. Results: All patients completed treatment. One patient included in the group 1 and none of the group 2 experienced grade 3 rectal toxicity (rectal ulcer). Seven patients in each group (4.0%) developed acute Grade 2 urinary symptoms, and none experienced urinary retention. No patient (0%) developed Grade 4 rectal complications or grade 3 or 4 urinary complications. With a median follow-up of 44 months, the 5-year actuarial PSA relapse-free survival rates for the whole group of patients was 95.7 %. No statistical differences between group 1 and 2 patients were found. Conclusions: High-dose IG-IMRT+HDR and HT was a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute and late rectal and urinary complications were significantly low, compared with what has been observed with high-dose conventional, 3D-conformal or IMRT-only. Short-term PSA control rates seem to be at least comparable to those achieved with 3D-EBRT or IMRT. Both treatment regimes were very effective. Longer follow-up is needed to know if better PSA control rate are achieved with longer HT. No significant financial relationships to disclose.

Concurrent chemoradiotherapy for locally advanced cervical cancer: Analysis of a single institutional 10-year experience

16056 Background: The purpose of this study was to report the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for the locally advanced cervical cancer in our institute. Methods: We retrospectively reviewed 147 patients (stage Ib: 9, II: 82, III: 80, and IVa: 7) with squamous cell carcinoma of the cervix treated with CCRT. Cisplatin (20mg/m2/day) was administered for 5 days every 3 weeks for a median of three courses (range: 1–5 courses) during radiotherapy (RT). The patients with paraaortic and/or common iliac lymphadenopathy were excluded. RT consisted of pelvic external beam RT (EBRT) with 40Gy/20 fractions followed by high-dose rate brachytherapy (HDR-BT) with 18Gy/3 fractions and pelvic EBRT with 10Gy/5 fractions using a midline block. Late complications were graded by the RTOG/EORTC criteria. Results: The 5-year actuarial overall survival (OS), disease-free survival (DFS), and pelvic relapse-free survival were 78.5%, 70.7%, and 78.0%, respectively. The 5-year OS by the disease stage was as follows: stage Ib 100%, II 82.0%, III 62.3%, and IVa 35.7%. Multivariate analysis identified pelvic lymphadenopathy, tumor diameter &gt; 7cm, and pretreatment hemoglobin &lt; 9.0g/dl as an independent prognostic factor for both OS and DFS. Only one patient suffered from grade 3 enterocolitis, but no grade 4 complication developed. Conclusions: Our experience suggests that CCRT using HDR-BT for locally advanced cervical cancer could achieve favorable local control without suffering from severe late complications. No significant financial relationships to disclose.

Breast cancer after treatment of Hodgkin disease: Clinical outcome of 38 cases in 27 patients

11059 Background: Many studies showed that women who are cured of HD have an increased risk of developing BC. Our purpose is to evaluate detection, pathology, management and prognosis of BC occurring after HD. Methods: Thirty-eight cases of BC in 27 survivors of HD were analyzed. All patients received supradiaphragmatic RT and 13 had also chemotherapy for HD. Results: The median age of the patients at diagnosis of HD was 25.5 years. The median interval to develop BC was 15.9 years. The median age at diagnosis of BC was 45.8 years. Ten women (37%) had bilateral disease; one of them had DCIS, 7 years before developing bilateral disease. Cancers were detected by mammography (59.4%), symptom presentation (24.3%), clinical examination (8%), and incidental during elective mastectomy (8%). Using Fisher’s Exact test, DCIS was more frequent (27%), where nodal involvement (29.6%), and ER positivity (81.5%) were paralleled that reported in general population. Thirty tumors (79%) were managed by mastectomy due to prior RT. Two women received RT following mastectomy. Eight tumors treated by lumpectomy, followed by RT in two women; one received whole breast RT, while the other received fractionated partial breast irradiation using 3D-conformal technique (50Gy/25 fractions) and she is doing well 1 1/2 years after RT. Adjuvant systemic therapy, given to 17 patients, was well tolerated. The median follow-up after BC was 61 months. Using Kaplan-Maier procedure, the 6-year actuarial relapse-free survival for node-negative BC after HD was 100%. Node positive patients had a significantly lower RFS of 58.3% ± 19% (P = 0.01). Conclusions: Compared to patients with primary BC, patients developing BC after HD are more likely to be younger, have bilateral disease and have more frequent DCIS. Other pathological features and prognosis are similar to that reported in general population. Patient awareness, breast examination and mammography should be part of the follow-up program for HD survivors. Mastectomy remains the standard of care in most of cases; however, lumpectomy followed by fractionated partial breast irradiation might be a reasonable approach to investigate for women who refuse mastectomy. No significant financial relationships to disclose.

HDR brachytherapy combined with hypofractionated EBRT for intermediate-high risk prostate cancer

14655 Background: To report on biochemical outcome and late complication in pts with localized prostate cancer (LPC) treated with HDR-brachytherapy (HDR-BT) combined with hypofractionated EBRT. Methods: From 06/2000 to 12/2004, 108 pts with intermediate (37 pts.) or high-risk (63 pts.) LPC were treated with hypofractionated EBRT (3 Gy × 17 fr., thrice a week) followed by HDR-BT (5 Gy × 5; 9 pts, 7 Gy × 3; 15 pts, 9 Gy × 2; 76 pts). HDR-BT was administered a week after the completion of the hypofractionated EBRT. The planning target volume was defined as the prostate gland with a 5-mm margin all around, and the planning was conducted based on CT images. Biologically effective doses (BED) to the prostate was between 83–84 Gy. All patient received androgen ablation. Acute and late toxicities were scored according to the EORTC/RTOG morbidity grading scales. Median follow-up duration was 27 months from HDR-BT and 39 months from initiation of androgen ablation. Results: All pts completed treatment. The 5-year actuarial PSA relapse-free survival rates for intermediate and high-risk pts were 100% and 93% respectively. Acute genitourinary (GU) toxicity was 64% in grade 0–1, 31% in grade 2 and 6% in grade 3. Urethral stricture developed in 3%, with a median time from the completion of HDR brachytherapy to the occurrence of 22 months (19–26 months). Ten pts had grade 2 rectal bleeding, with a median time from the completion of HDR brachytherapy to the occurrence of 11 months (7–14 months). No pts developed grade 3 or more severe rectal complication. The incidence of acute and late toxicity did not differ according to the fractionation schema of HDR-BT. Conclusion: Our data demonstrate the successful feasibility of HDR-BT combined with hypofractionated EBRT as a safe method for escalating the total dose to the prostate without significant increasing risk of acute and late GU and rectal toxicities. No significant financial relationships to disclose.

Surveillance of stage I testicular seminoma: British Columbia Cancer Agency Experience 1992 to 2002

Objectives To review the changes in the use of surveillance in Stage I seminoma in British Columbia during the past decade and to compare the relapse rates provincially against those in published reports. Postorchiectomy surveillance of Stage I seminoma is an alternative to adjuvant radiotherapy. The relapse rate from a pooled surveillance series was 18% at 5 years. Methods We reviewed the British Columbia Cancer Agency Tumour Registry records for all cases registered with a diagnosis of seminoma of the testes referred to the BCCA between 1992 and 2002. Patients not treated with radiotherapy within 4 months of referral were reviewed for patient and disease parameters (age, rete testes invasion, size, lymphatic invasion), relapse, salvage treatment, and survival. Results A total of 458 patients with Stage I seminoma were identified. Of these, 93 went onto surveillance. The annual percentage of patients going onto surveillance increased from 10% in 1992 to 33% by 2002. The median follow-up was 33 months. The 5-year actuarial relapse-free survival rate was 78%. Relapse was more common in those with known adverse prognostic factors (rete invasion or size greater than 4 cm). The actuarial 5-year relapse free rate was 86%, 71%, and 50% for patients with no risk factor, one risk factor, or both risk factors, respectively. The disease-specific survival rate at 5 years was 96%. Conclusions Surveillance of patients with seminoma in British Columbia increased between 1992 and 2002. The relapse and survival rates in this population-based series were similar to those previously reported.

Orbital marginal zone B-cell lymphoma of MALT: Radiotherapy results and clinical behavior

To elucidate the clinical behavior and treatment outcome of low-grade primary orbital lymphoma arising from mucosa-associated lymphoid tissue (MALT). Forty-eight patients with pathologically confirmed marginal zone B-cell lymphoma of MALT were treated with radiotherapy (RT). Thirty-eight patients (79.1%) received thorough staging workup studies including bone marrow biopsy. Radiation doses ranged from 5.4 to 30.6 Gy (median, 30.6 Gy). Median follow-up period was 70 months. Only 2 patients revealed extraorbital lymphoma involvement (bone marrow, skin). Forty-six of 52 eye lesions showed complete response to RT. Six lesions demonstrated a partial response and showed gradual regression during the follow-up period of 39-72 months. Three patients experienced local recurrences at 34, 48, and 52 months after RT, which seemed to be related to improper use of the lens shield. Salvage re-RT was successful. The 10-year actuarial relapse-free survival, cause-specific survival, and overall survival rates were 93.1%, 97.9%, and 86.9%, respectively. Most of the MALT lymphoma of the orbit was localized at diagnosis and extraorbital relapse rarely occurred. Therefore, extensive staging workup at the time of diagnosis and follow-up studies to detect distant relapse may not be obligatory. Low-dose RT alone with proper lens shielding is the optimum treatment modality for orbital MALT lymphoma.