Median Duration Of Local Control Research Articles

Palliative High-Dose Radiotherapy for Ulcerative Breast Lesions

<h3>Purpose/Objective(s)</h3> Breast cancer with skin invasion may cause decreased quality of life due to bleeding, self-destruction, and pain. However, there is no consensus on the optimal dose for palliative irradiation. In this study, we investigated the efficacy and safety of relatively high-dose treatment to sustain tumor control and symptom relief in patients with long-term survival expectations. <h3>Materials/Methods</h3> Between June 2013 to April 2021, a total of 32 patients who received relatively high-dose palliative irradiation for breast cancer with skin invasion at our institution were selected. Radiotherapy was performed at a total dose of 45-70 Gy with 2-3 Gy per fraction. (45 Gy/15 Fr:1, 50 Gy/20 Fr:3, 54 Gy/18Fr:1, 60 Gy/24 Fr:4, 60 Gy/20 Fr:19, 60 Gy/30 Fr:2, 70 Gy/35 Fr:2) We retrospectively analyzed the efficacy of local control, symptomatic relief, and adverse events. <h3>Results</h3> Median follow-up was 9.0months (range:2.6-69.6months). The median age was 65years (range: 36-89years), 27 cases (84%) had distant metastasis at the time of radiotherapy. After radiotherapy, 29 cases (91%) had symptomatic relief of bleeding, discharge, or pain. Of the 30 cases in which CT was taken, 28 cases (93%) showed tumor reduction, of which 6 cases showed subsequent re-growth. The median duration of local control was 4.9months (range: 1.23-68.87months), and the 6-month local control rate was 86.9%, 12-month local control rate was 68.3%, and 24-month local control rate was 60.7%. Acute adverse events included dermatitis in G3/G2/G1 = 13/14/5 cases (40/44/16%), and late adverse events included pneumonitis in G2/G1 = 1/15 cases (3/47%). No other late adverse events above G3 were observed. <h3>Conclusion</h3> The local control and symptom relief of relatively high-dose therapy are favorable. The frequency of late adverse events, such as pneumonitis, is within an acceptable range. Further investigation on prescription dose and safety is required.

Examining the Use of Radiation Therapy for Cholangiocarcinoma: Benefits through Modern Techniques

Background: Cholangiocarcinoma (CCA) is a rare malignant tumor of the bile duct epithelium. At first diagnosis, only a minority of patients are eligible for surgery, which is regarded as the only curative treatment. This study examines the role of radiation therapy (RT) and chemoradiotherapy (CRT) in the definitive and adjuvant treatment situation. Methods: The monocentric, retrospective analysis included 39 patients with CCA undergoing 53 RT courses. Data were collected from January 2005 to September 2018. There were 11 cases of CRT, 6 of which were definitive. Surgery was either palliative (n = 6) or radical (n = 15). Results: After RT, the median overall survival (OS) was 10.4 months (m), median progression-free survival was 5.6 m, and median duration of local control (DOLC) was 8.9 m. There was a significant difference in survival between patients with and without locoregional lymph node metastasis (OS: 4.3 vs. 15.4 m, p = 0.031). After treatment of a primary tumor, DOLC was about twice as long as in the recurrent situation (10.4 vs. 5.4 m, p = 0.032). Conservative therapy significantly elevated the risk of local recurrence compared to radical surgery in univariate and multivariate analyses. Side effects were mostly classified as mild to moderate. Termination of RT and increased alanine aminotransferase were significantly less frequent after stereotactic body radiation therapy and hypofractionation. Conclusion: RT can achieve local control in patients with CCA. Toxicities of RT are manageable but require close clinical and laboratory follow-up.

Long-Term Survival and Local Control Outcomes in Oligometastatic Colorectal Cancer Treated with Liver Stereotactic Body Radiation Therapy

The purpose of the present study was to evaluate clinical outcomes following stereotactic body radiation therapy (SBRT) in patients with liver metastases (LM) due to colorectal cancer (CRC). This was a single-institution retrospective study of patients included in a prospectively maintained institutional database. Outcome endpoints included overall survival (OS) and local control (LC). We also performed assessments for predictors of LC and OS including evaluation of BED10 less than or greater than 150. Eligible patients had LM due to CRC, were treated with SBRT between 2007-2018, and had at least 3 months of follow up. Median SBRT dose was 54 Gy (range 32-60 Gy) in 3 fractions (range 3-5), and median BED10 was 151.0 Gy. All survival times were calculated from the start date of SBRT. Kaplan-Meier curves were used to estimate actuarial survival times, and Cox regression was used for multivariable analysis (MVA) of predictors of OS. We identified 67 eligible patients and 15/67 (22%) of patients had prior partial hepatectomy. Median number of chemotherapy regimens prior to SBRT was 1 (range 0-3). The majority of patients (79.6%) had a solitary liver metastasis; 2 had extrahepatic disease at the time of SBRT. The maximum number of treated LM was 3. Median tumor diameter was 2.7 cm (range 0.4-5.6). At a median follow up of 42.5 mos (range 3-96), 27/67 patients (40.2%) of patients had died. The median estimated OS (KP method) in this patient cohort was 64.0 months (95% CI 41.6 - Not Estimable (NE)). Estimated median KP duration of local control was 71.4 months (95% CI: 38.5, NE) in the entire patient cohort. Duration of local control was statistically significantly better in patients with liver SBRT treatment where the BED was > 150. The median duration of LC in patients with liver SBRT plans with BED10 > 150 was 74.4-months (95% CI: 40.1, NE) vs 26.1 month (95%: CI 11.6 – NE) in those with liver SBRT plan with BED < 150 (p=0.0006). The median KP estimated OS was 82.4 months (95% CI: 41.4 – NE) in patients with SBRT plan > 150 vs 62.8 months (95% CI: 36.2 mo. – NE) in those with BED < 150 (p= 0.697). Duration of local control was found to significantly correlate with OS. The hazard of death was reduced by 5.1% for each additional month of local control. GTV size (cc), diameter of treated metastases, and presence of K-ras mutation did not appear to be a predictor of LC in our patient cohort. SBRT is very effective in the management of hepatic oligometastases and was associated with an estimated median OS greater than 5 years in select patients. In this study, we found that duration of local control was significantly associated with overall survival. Additionally, it appears from this series that BED10 > 150 is associated with increase in local control.

Efficacy and Prognosis of CT-Guided Implantation of 125I Seeds As Salvage Treatment for Recurrent Nasopharyngeal Carcinoma after External Beam Radiotherapy--a Long-Term Experience at a Single Institution

To assess the safety and efficacy of computed tomography (CT)-guided 125I seeds implantation for recurrent nasopharyngeal carcinoma (NPC) after external beam radiotherapy (EBRT). Twenty-nine patients with recurrent NPC (thirty-nine lesions) after EBRT from February 2003 to December 2017 were enrolled. All the patients experienced preoperative assessment, patient immobilization, and CT scan, preoperative planning, 125I seeds implantation, postoperative dosimetry assessment, and postoperative care. Median radioactivity of 125I seeds was 0.61 (range, 0.22-0.79) mCi. Median number of implanted seeds was 34 (3-83). Median value of D90 was 136 (62.4-246) Gy. The adverse event was evaluated by the Radiation Therapy Oncology Group (RTOG) classification criteria. Overall survival (OS), local control (LC), local progression-free survival (LPFS), were investigated for their relationship with the prognosis. Median duration of follow-up was 13.7 (4.4-71.2) months. Median duration of LC was 31.6 (2.1-60.2) months. LC at 1, 3, and 5 years was 69.0%, 46.7% and 18.7%, respectively. Median duration of OS was 33.4 (4.4∼71.2) months. OS at 1-, 3- and 5-years was 73.8%, 40.8% and 40.8%, respectively. Median duration of LPFS was 22.6 (3.0-60.2) months. LPFS at1-, 3- and 5-years was 72.0%, 38.7% and 38.7%, respectively. Univariate analysis suggested that sex(P=0.048) and frequency of previous external beam radiotherapy (P=0.018) were prognostic factors influencing survival without local recurrence. Moreover, sex (P=0.023), frequency of previous EBRT (P=0.001), time from the first EBRT to seeds implantation (P=0.007), and D90 (P=0.049) were prognostic factors influencing LC. Multivariate retrospective analysis indicated that sex (P=0.03) was an independent prognostic factor for survival without local recurrence. Prevalence of side effects (≥grade 3) was 20.7%. 125I seeds implantation was a safe and feasible salvage treatment for recurrent NPC after EBRT.

Application of CO 2 Laser Evaporation in Locally Advanced Melanoma

Aim:This study aims to investigate the role of CO2 laser evaporation in the treatment of melanoma patients with satellite or in-transit metastases.Materials & methods:Patients who underwent CO2 laser evaporation were retrospectively included between November 2002 and August 2018. The Sharplan 40C CO2 laser was used with a high pulse wave mode. Data concerning patient and tumor characteristics, CO2 laser evaporation and subsequent therapies were collected.Results:A total of 26 patients were included. Median duration of local control was 5.5 months. The median number of lesions evaporated per treatment was three (1–16); patients received a median of three (1–19) treatments.Conclusion:In a selected group of melanoma patients with satellite or in-transit metastases, CO2 laser evaporation should be considered as treatment for local control.

Intensity Modulated Radiotherapy is a Well-Tolerated and Effective Treatment for the Long-Term Control of Intra-Abdominal and Retroperitoneal Oligometastatic Renal Cell Cancer

Background: The use of conventionally fractionated intensity modulated radiotherapy (IMRT) in the management of oligometastatic renal cell carcinoma (RCC) is currently poorly characterised in the literature. Objective: To evaluate the safety and effectiveness of IMRT for intraabdominal and retroperitoneal RCC oligometastases. Methods: Retrospective analysis of 14 patients with oligometastatic RCC treated with IMRT with the aim of inducing long-term control. Indications for radiotherapy included bleeding abdominal mass (5 patients), solitary renal bed recurrence (5 patients) and isolated, asymptomatic pancreatic mass (4 patients). The prescribed radiotherapy dose was 50 Gray in 20 to 25 fractions. Patients were followed up long-term using regular cross-sectional imaging and clinical review to assess local and distant disease control and treatment related toxicity. Results: At median follow up of 33.5 (6–68) months, 12 patients remain alive (86%), of whom 11 (92%) have no evidence of local recurrence. Six patients (43%) developed further metastatic disease, of whom 4 (67%) received systemic treatment. Median duration of local control was 33.5 months, and 1- and 3-year overall survival (OS) was 92.9% and 85.7% respectively. No treatment-related toxicities ≥ grade 3 and no long-term sequelae were observed. Conclusions: IMRT to intra-abdominal and retroperitoneal metastasis in oligo-metastatic RCC can be delivered safely, provide durable responses and excellent longer-term survival if given to a sufficiently high dose over a conventionally fractionated course. Our study is the first to date with long-term follow up to evaluate the role of IMRT in such cases and has important implications for treatment of oligometastatic RCC.

Radiotherapy for extramedullary leukaemic manifestation (Chloroma).

Extramedullary leukaemic disease (EMD, synonym chloroma) is arare solid manifestation of myeloid leukaemia for which the value of radiotherapy (RT) as atreatment strategy remains controversial. The aim of this study is to analyse the effectiveness of various RT doses for EMD in the modern treatment era. Between January 2000 and June 2016, 20patients with total of 45lesions underwent RT for EMD at our institution. With amedian radiation dose of 26 Gy (range 4-42 Gy), local remission could be achieved in 91% of patients (complete remission rate: 71%). The median duration of local control (DOLC) was 17months (95%confidence interval [CI] 0.5-33) and the median overall survival (OS) after chloroma onset was 24months (95%CI 11-38). No noticeable difference between high- and low-dose regimens has been observed (74% versus 68%; P= 0.5). In the multivariate analysis, only Eastern Cooperative Oncology Group (ECOG) score and bone marrow state during RT have proven to be determinant for durable local control and OS. Low-dose RT (≤26 Gy) achieves good local control compared to high-dose regimes. Bone marrow state during RT and ECOG score during RT may play acrucial role, influencing both DOLC and OS.

The effectiveness of radiotherapy for leukemia cutis.

Leukemia cutis (LC) is a rare clinical presentation of leukemia that is associated with poor prognosisabs. To date, the value of radiotherapy (RT) for the treatment of LC remains controversial. Therefore, the aim of this study was to analyse the effectiveness of various RT doses for LC. Between January 2000 and January 2016, 13 patients underwent RT at our institution after exhibiting progressive disease following other treatment modalities. A total of 36 radiation courses were administered to 13 patients (8 females, 5 males) with a median age of 41years (range 2-76). Radiation modalities included 32 focal treatments, while total skin electron beam therapy was applied to four patients. The median RT dose was 27Gy (range 8-34). A complete response rate (CRR) to RT was achieved for 32/36 (89%) lesions (100% for AML lesions versus 33% for the other leukemias; P < 0.001). The median duration of local control (DOLC) for the entire cohort was 38months (range 0-98), while the median survival (MS) from the time of LC presentation was 13months (range 2.5-106). The CRR for the LC lesions treated with high-dose regimens (>26Gy) versus low-dose regimens (≤26Gy) was 95 versus 83%, respectively (P = 0.26), and the median DOLC was 44months versus 10months, respectively (P = 0.019). AML patients had a better long-term outcome than the other patients according to median DOLC (40months versus 2months, respectively; P < 0.001) and MS (24 versus 6months, P = 0.004). RT was well tolerated without significant adverse events. A radiation dose ≤26Gy confer a comparable CRR to high-dose regimens and appears to be an effective treatment for controlling LC progression. However, radiation doses >26Gy were associated with a longer DOLC. LC patients with underlying AML are associated with better outcome compared with other types of leukemia.

A matched pair analysis of five-fraction stereotactic body radiation therapy versus protracted conventional radiation therapy in patients receiving chemotherapy for locally advanced pancreatic cancer.

444 Background: Stereotactic body radiation therapy (SBRT) is a novel treatment modality for unresectable, locally advanced pancreatic cancer (LAPC). SBRT delivers high doses of radiation over a shorter duration, with minimal acute toxicities, compared with conventional radiation therapy (CRT) using intensity modulated radiation therapy (IMRT) or 3D conformal techniques (3D-CRT). Few studies have compared outcomes between SBRT and CRT techniques. We conducted a retrospective matched pair analysis of LAPC patients receiving chemotherapy and either SBRT or CRT to assess local control (LC), progression-free survival (PFS), and overall survival (OS). Methods: We retrospectively analyzed 28 patients with LAPC who were treated between August 2006 and August 2014 with 5-FU- or gemcitabine-based chemotherapy combined with CRT (45–56 Gy over 25–28 fractions) or SBRT (25–30 Gy over 5 fractions). Fourteen patients treated with CRT were matched with 14 patients treated with SBRT for age (&lt; 65 vs. ≥ 65 years); nodal staging (N0 or N1); and chemotherapy type (gemcitabine-based or 5-FU-based, administered either concurrently or as induction therapy). Tumor response was assessed using RECIST and all outcomes were calculated from the date of diagnosis. The Log Rank test of Kaplan-Meier curves was used for statistical analyses. Results: Median follow-up time was 11 months (mo). The median duration of LC, PFS, and OS for the entire cohort was 11, 8, and 14 mo, respectively. Median duration of LC was 10 mo for CRT and 11 mo for SBRT (p &gt; 0.05). Median PFS was 8 mo for both groups (p &gt; 0.05). The median OS times were 12 mo for SBRT and 16 mo for 3D-CRT/IMRT (p &gt; 0.05). Conclusions: In this small matched-pair analysis, LAPC patients treated with chemotherapy had similar outcomes following 5 fractions of SBRT as compared with a protracted course of CRT. Given the shorter treatment duration with SBRT, further study is warranted with increased cohort sizes and stratification by other patient and disease characteristics.

Palliative split-course hypofractionated radiotherapy for incurable mucosal squamous cell head and neck cancer: a 10 year experience

AbstractIntroductionLocally advanced head and neck cancer can be a distressing disease due to a variety of reasons. This retrospective study looks at the tolerability and outcomes for palliative split-course hypofractionated radiotherapy for this group of patients treated in our centre.ResultsA total of 59 patients were treated with hypofractionated split-course radiotherapy for incurable mucosal squamous cell carcinoma of the head and neck region in our centre over a 10-year period. In all, 71% had stage IV disease. Radiotherapy consisted of three phases of 14·4 Gy/phase, in four to eight fractions over 4 days giving one·8–3·6 Gy/fraction. The phases were separated by 2 weeks. A total of 40 patients (63%) completed all three phases. A total of 72% patients had no acute toxicities and the palliation rate was 83% (complete and partial). Only five patients had no meaningful palliation having completed all three phases. Median duration of local control was 6 months (range: 1–63 months) and median overall survival was 8 months (range: 1–68 months). In five patients, the control was durable with no recurrence at the time of analysis with survival ranging from 6 to 57 months.ConclusionWe are the first UK centre to report with long-term data, the use of a palliative three phase regime that provides meaningful palliation with acceptable toxicities. In addition, for some patients, it has resulted in durable long-term control.

Cetuximab in the treatment of head and neck cancer: preliminary results outside clinical trials

The purpose of this study was to evaluate the clinical efficacy in our daily practice, outside clinical trials, of cetuximab plus radiotherapy in a majority of treatment-naive patients with locoregionally advanced head and neck squamous cell carcinomas. A retrospective study was performed to evaluate outcomes in patients who were treated definitively with cetuximab and radiotherapy (ExRT). Patients with stage III or IV, nonmetastatic, measurable squamous cell carcinoma of the head and neck (SCCHN) were eligible. There were 18 males and two females. The median age was 61 years (range from 49 to 87 years old). Concurrent radiotherapy and cetuximab was used, in first line, in 17 patients with locally advanced disease; two patients with recurrent SCCHN, who were intolerant of Cisplatin-based regimens, were treated with radiotherapy combined with weekly cetuximab; and 1 patient received cetuximab and radiotherapy postoperatively. The median time of response was 10 months (range from 2 to 24 months). A partial response was observed in 11 cases; a complete response in nine cases. The occurrence of grade 2-3 skin toxicity was observed in 11 cases. Skin toxicity was clearly correlated with a better response and the duration of the response to the treatment. The use of cetuximab in combination with radiotherapy does not increase the side effects of radiotherapy. At the end of the follow-up, 17 patients died. Cetuximab, with its highly targeted mechanism of action and synergistic activity with current treatment modalities, is a valuable treatment option in head and neck patients. The effect of the epidermal growth factor receptor antagonist occurs without any change in the pattern and the severity of toxicity usually associated with head and neck radiation. Cetuximab seems not to provide the most benefit for patients with oropharyngeal cancers but will in patients with T4 tumors. However, the median duration of local control was less as described in the clinical trials.

Cetuximab in the treatment of head and neck cancer: preliminary results outside clinical trials

Cetuximab in the treatment of head and neck cancer: preliminary results outside clinical trials Didier Dequanter, Mohammad Shahla, Pascal Paulus, Phillippe LothaireDepartment of Head and Neck Surgery, CHU Charleroi, Montigny le Tilleul, BelgiumIntroduction: The purpose of this study was to evaluate the clinical efficacy in our daily practice, outside clinical trials, of cetuximab plus radiotherapy in a majority of treatment-naive patients with locoregionally advanced head and neck squamous cell carcinomas.Methods: A retrospective study was performed to evaluate outcomes in patients who were treated definitively with cetuximab and radiotherapy (ExRT). Patients with stage III or IV, nonmetastatic, measurable squamous cell carcinoma of the head and neck (SCCHN) were eligible.Results: There were 18 males and two females. The median age was 61 years (range from 49 to 87 years old). Concurrent radiotherapy and cetuximab was used, in first line, in 17 patients with locally advanced disease; two patients with recurrent SCCHN, who were intolerant of Cisplatin-based regimens, were treated with radiotherapy combined with weekly cetuximab; and 1 patient received cetuximab and radiotherapy postoperatively. The median time of response was 10 months (range from 2 to 24 months). A partial response was observed in 11 cases; a complete response in nine cases. The occurrence of grade 2&ndash;3 skin toxicity was observed in 11 cases. Skin toxicity was clearly correlated with a better response and the duration of the response to the treatment. The use of cetuximab in combination with radiotherapy does not increase the side effects of radiotherapy. At the end of the follow-up, 17 patients died.Conclusion: Cetuximab, with its highly targeted mechanism of action and synergistic activity with current treatment modalities, is a valuable treatment option in head and neck patients. The effect of the epidermal growth factor receptor antagonist occurs without any change in the pattern and the severity of toxicity usually associated with head and neck radiation. Cetuximab seems not to provide the most benefit for patients with oropharyngeal cancers but will in patients with T4 tumors. However, the median duration of local control was less as described in the clinical trials.Keywords: head and neck cancer, epidermal growth factor receptor antagonist, radiotherapy, clinical trials

58 Painful osteolytic lesions by multiple myeloma: Effectiveness and timing of radiotherapy in a multimodal approach

Background: Between 1979 and 1989, 48 cases of extradural spinal cord and cauda equina compression in patients with lymphoma (24) and myeloma (24) received local radiation therapy for control of cord compression. Twenty five (52%) of the cases were treated by surgical decompression prior to irradiation. Thirty five (73%) of the cases received chemotherapy following the diagnosis of spinal cord compression. Post-treatment outcome was assessed at a minimum follow-up of 24 months to determine the significant clinical and treatment factors following irradiation.Results: Seventeen (71%) of the lymphoma and 15 (63%) of the myeloma patients achieved local control, here defined as improvement to, or maintenance of ambulation with minimal or no assistance for 3 months from the start of radiotherapy. At a median follow-up of 30 (2–98) for the lymphoma and 10 (1–87) months for the myeloma patients, the results showed that survival following local radiation therapy for cord compression was independently influenced by the underlying disease type in favour of lymphoma compared to myeloma (P < 0.01). The median duration of local control and survival figures were 23 and 48 months for the lymphomas compared to 4.5 and 10 months for the myeloma cases. Survival was also independently influenced by preservation of sphincter function at initial presentation (P < 0.02) and the achievement of local control following treatment (P < 0.01).Discussion: We conclude that while disease type independently impacts on outcome following treatment of spinal cord compression in lymphoma and myeloma, within both of these disease types the achievement of local control of spinal cord compression is an important management priority, for without local control survival may be adversely affected.

GOFURTGO trial (GFG): An AGITG multicenter phase II study of fixed dose rate gemcitabine-oxaliplatin (Gem-Ox) integrated with concomitant 5FU and 3-D conformal radiotherapy (5FU-3DRT) for the treatment of locally advanced pancreatic cancer (LAPC)

4616 Background: Our previous study of Gem with sandwich 5FU-3DRT for LAPC was encouraging (Br J Cancer 2007: 97, 464–471). Gem-Ox has higher response rate than Gem, improved progression free survival (PFS) but not overall survival (OS). Its use in LAPC may improve local control (LC) and delay systemic spread. GFG is a study of induction (ind) Gem-Ox, then 5FU-3DRT, then consolidation (con) Gem-Ox. Primary outcome is feasibility using proportion of patients (pts) receiving &gt; 80% planned dose for each component. Secondary outcomes are safety, activity and QOL. Methods: Pts with previously untreated inoperable LAPC, M0, measurable disease, ECOG 0–2 were given Gem (1000mg/m2 d1 + d15 q28), Ox (100mg/m2 d2 + d16 q28) in both ind (1 cycle) &amp; con (3 cycles), &amp; 5FU 200mg/m2/d over 6 weeks during RT of 54Gy in 30 fractions of 1.8Gy. Results: 48 pts were enrolled, median age 61y (44–81y), PS 0/1=96%, regional lymph nodes=44%, T4=46%. Worst grade (G) for anaemia (10%); fatigue, nausea (8%); diarrhoea, vomiting, neutropenia, infection (4%); stomatitis, anorexia (2%) was G3. Thrombocytopenia was G3=2% G4=2%; liver function was G3=23% G4=6%; late radiation toxicity was G3=2% G4=2% (both gastric bleeding). Half of all pts completed all planned cycles (24 pts); 29% of pts received &gt;80% of all treatment (14 pts); 70% of pts received &gt;80% of all chemoradiation (33 pts). Pts ceased treatment for toxicity (16%), PD (21%) or doctor/pt preference (4/2%). Global QOL did not significantly change from baseline. Median duration of LC, PFS, OS were 15.8, 9.9, 15.4m at median follow up of 29.7m. Exploratory analysis of age, disease stage, PS, CA19–9 or WCC found no univariate predictors of PFS or treatment completion. 8/48 pts survived &gt;24m. Conclusions: Compared to our previous study using the same radiation schedule, addition of oxaliplatin was associated with improved LC, PFS &amp; OS (prev. 11.9, 7.1 &amp; 11.7m) without significant offset by toxicity. The extended duration of LC and a subset who had a very prolonged benefit may be due to patient selection but equally may suggest an incremental benefit from more intensive systemic therapy requiring further study in controlled trials. [Table: see text]

Phase II study of capecitabine (X) plus reirradiation in patients (pts) with recurrent squamous cell carcinoma of the head and neck (SCCHN)

15504 Background: X has shown substantial activity in SCCHN [Pivot et al. 2004] and is replacing 5-FU as the backbone of chemotherapy in a wide range of solid tumors, particularly colorectal cancer. In addition, X has a unique survival benefit in breast cancer. There is substantial data to support using X in chemoradiation [Dunst et al. 2004]. We evaluated the therapeutic impact and safety profile of X plus reirradiation in SCCHN. Methods: Pts with locally advanced unresectable SCCHN who had prior radiotherapy (RT, with or without chemotherapy) received X 450 mg/m2 twice daily, 7 days a week. RT was delivered as a standard fractionated regimen (2 Gy/day, 5 fractions/week) up to a total dose of 50–70 Gy. The cumulative (life-time) dose within overlapping fields was not to exceed 120–130 Gy. Results: Currently, 20 male pts have completed treatment. Baseline characteristics were: median age 57 (42–72), ECOG PS 0/1 5/15. Six pts had previous chemoradiation followed by radical resection; 4 had surgery and postoperative RT; 10 had concomitant chemoradiation (accelerated and hyperfractionated). Twelve pts experienced locoregional recurrences, 4 developed secondary primaries, and 4 had a regional lymph node relapse. The median time since prior radiation therapy was 16 (8–244) months. Efficacy (as evaluated by WHO criteria): 7 pts (35%) had a complete (2) or partial (5) response; stable disease was observed in 11 pts, and tumor progression immediately after therapy was observed in 2 pts. Median duration of local control and median survival will be presented at the meeting. The most frequently observed toxicity was mucositis, which was grade 3 in only 2 pts; grade 1 or 2 skin reaction was seen in 9 pts. There was no evidence of systemic toxicity or myelosuppression, probably due to the very low dose of X. RT was completed without delay in all pts, and X was interrupted prematurely in 2 pts due to grade 3 mucositis. Conclusions: Our preliminary data suggest that X chemoradiation is a well-tolerated and effective treatment modality for previously irradiated pts with SCCHN. Based on available data, a higher dose of X should be feasible and potentially more effective. Earlier use of X in SCCHN could also be evaluated. [Table: see text]

Is gross-total resection sufficient treatment for posterior fossa ependymomas?

The goals of this study were to analyze outcomes in patients with posterior fossa ependymomas, determine whether gross-total resection (GTR) alone is appropriate treatment, and evaluate the role of radiation therapy. All patients with newly diagnosed intracranial ependymomas treated at Barrow Neurological Institute between 1983 and 2002 were identified. Those with supratentorial primary lesions, subependymomas, or neuraxis dissemination were excluded. Forty-five patients met the criteria for the study. Gross-total resection was accomplished in 32 patients (71%) and subtotal resection (STR) in 13 (29%). Radiation therapy was given to 25 patients: 13 following GTR and 12 after STR. The radiation fields were craniospinal followed by a posterior fossa boost in six patients and posterior fossa or local only in the remaining patients. With a median follow-up period of 66 months, the median duration of local control was 73.5 months with GTR alone, but has not yet been reached for patients with both GTR and radiotherapy (p = 0.020). The median duration of local control following STR and radiotherapy was 79.6 months. The 10-year actuarial local control rate was 100% for patients who underwent GTR and radiotherapy, 50% for those who underwent GTR alone, and 36% for those who underwent both STR and radiotherapy, representing significant differences between the GTR-plus-radiotherapy and GTR-alone cohorts (p = 0.018), and between the GTR-plus-radiotherapy and the STR-plus-radiotherapy group (p = 0.003). There was no significant difference in the 10-year actuarial local control rate between the GTR-alone and STR-plus-radiotherapy cohorts (p = 0.370). The 10-year overall survival was numerically superior in patients who underwent both GTR and radiotherapy: 83% compared with 67% in those who underwent GTR alone and 43% in those who underwent both STR and radiotherapy. These differences did not achieve statistical significance. Univariate analyses revealed that radiotherapy, tumor grade, and extent of resection were significant predictors of local control. Gross-total resection should be the intent of surgery when it can be accomplished with an acceptable degree of morbidity. Even after GTR has been confirmed with postoperative imaging, however, adjuvant radiotherapy significantly improves local control. The authors currently recommend the use of postoperative radiotherapy, regardless of whether the resection is gross total or subtotal.

Omental transposition flap for gross locally recurrent breast cancer.

The omentum has been employed to cover the defect produced after resection of gross breast cancer recurrence for nearly three decades. A series of 11 patients undergoing omental transposition flap for very wide resection of gross local recurrence (LR) of breast cancer is reported. The median age was 39 years, with a short interval (median = 21 months) from the treatment of the primary tumour to LR. Local recurrence was gross and predominantly inflammatory. All except one patient had lymphovascular invasion in the recurrent tumour. The omental graft was 100% viable but one patient required re-application of further split-thickness skin graft. The mean hospital stay was 16 days. Two cases of seroma formation were encountered. New recurrence developed around the periphery of the flap in eight patients after a median duration of local control of only 2.5 months. Eight patients died with metastatic disease after a median period of 6 months, six patients with uncontrolled local disease. Five patients were free from LR in over half of their remaining period of life. Omentoplasty is a safe and reliable procedure but the length of palliation achieved is often far from satisfactory.

Local control and survival in spinal cord compression from lymphoma and myeloma

Background: Between 1979 and 1989, 48 cases of extradural spinal cord and cauda equina compression in patients with lymphoma (24) and myeloma (24) received local radiation therapy for control of cord compression. Twenty five (52%) of the cases were treated by surgical decompression prior to irradiation. Thirty five (73%) of the cases received chemotherapy following the diagnosis of spinal cord compression. Post-treatment outcome was assessed at a minimum follow-up of 24 months to determine the significant clinical and treatment factors following irradiation. Results: Seventeen (71%) of the lymphoma and 15 (63%) of the myeloma patients achieved local control, here defined as improvement to, or maintenance of ambulation with minimal or no assistance for 3 months from the start of radiotherapy. At a median follow-up of 30 (2–98) for the lymphoma and 10 (1–87) months for the myeloma patients, the results showed that survival following local radiation therapy for cord compression was independently influenced by the underlying disease type in favour of lymphoma compared to myeloma ( P < 0.01). The median duration of local control and survival figures were 23 and 48 months for the lymphomas compared to 4.5 and 10 months for the myeloma cases. Survival was also independently influenced by preservation of sphincter function at initial presentation ( P < 0.02) and the achievement of local control following treatment ( P < 0.01). Discussion: We conclude that while disease type independently impacts on outcome following treatment of spinal cord compression in lymphoma and myeloma, within both of these disease types the achievement of local control of spinal cord compression is an important management priority, for without local control survival may be adversely affected.

A prospective randomized comparison of radiation therapy plus lonidamine versus radiation therapy plus placebo as initial treatment of clinically localized but nonresectable nonsmall cell lung cancer

Purpose : By means of a multicenter, prospective randomized, placebo-controlled study, to assess the impact of adding the radiation-enhancing agent lonidamine to standard “curative-intent” radiation therapy upon overall survival, progression-free survival, and local progression-free survival of patients with clinically localized but nonresectable nonsmall cell lung cancer. Methods and Materials : Lonidamine, or the lonidamine-placebo, was administered at a dose of 265 mg/m 2 in three divided daily doses. Drug therapy began 2 days prior to the initiation of radiation therapy and continued until progression of disease mandated a change in therapy. The radiation therapy dose was 55–60 Gy, at a daily dose of 1.8 Gy and five treatments per week. Patients with clinical Stage II or III nonsmall cell lung cancer were stratified within the treatment center, and within two histologic strata: epidermoid vs. other nonsmall cell cancers. Results : A total of 310 patients were enlisted on study, 152 on the placebo arm and 158 on the lonidamine arm. The median survival durations were 326 days and 392 days for the placebo and lonidamine-treated groups respectively, p = 0.41 for a comparison of the survival curves. Median progression-free survival and median local progression-free survival durations were 197 days and 341 days for placebo + radiation therapy vs. 230 days and 300 days for lonidamine + radiation therapy; p-values for the respective curves were 0.75 and 0.42. Although there were proportionately more lonidamine-treated patients than placebo-treated patients demonstrating continued local control in excess of 12 months, the numbers of patients still at risk after 24 months were too small for meaningful statistical analysis. Conclusion : This multicenter Phase III study failed to demonstrate a significant advantage in the lonidamine-treated population in overally patient survival, in progression-free survival, or in the median duration of local control.

Interstitial thermoradiotherapy with ferromagnetic implants for locally advanced and recurrent neoplasms

Purpose : The University of Arizona, University of California at San Francisco, City of Hope Medical Center, and University of Wisconsin participated in a Phase I/II protocol to assess the heating ability and the toxicity of interstitial thermoradiotherapy using ferromagnetic implantation. Methods and Materials : Forty-four patients with advanced primary or recurrent extra-cranial solid malignancies were enrolled in this study. Fourteen gauge catheters were implanted into tumors and, once in the department of Radiation Oncology, loaded with ferromagnetic seeds to deliver a 60 min hyperthermia treatment. Multi-point thermometry was continuously used throughout the heating sessions for all patients, sampling the periphery as well as the core of the tumor. After 192Iridium brachytherapy, 18 patients then had an additional treatment. The mean radiation dose while on protocol was 50.0 Gy, with total doses (including prior radiotherapy) ranging from 20.3–151.8 Gy (median = 88.7 Gy). Response and toxicity were assessed by inspection, palpation, and/or radiologic studies. Forty-one patients were evaluable for response, and there were 55 analyzable hyperthermia treatment sessions. Results : The complete response rate was 61% (25/41). The partial response rate was 31.7% and only 7.3% failed to respond. Median duration of local control has not yet been reached. The mean maximum, minimum, and mean time-averaged temperatures for all in-tissue sensors were 43.7°C, and 41.0°C, respectively. Tumor size was the only factor significantly correlated with temperatures or with complete response rate; larger tumors attained higher temperatures but smaller tumors had a higher response probability. Nineteen patients (43%) experienced toxicities, however there was only a 7% (3/44) rate of serious complications (Grade 3 or 4). Prior treatment with hyperthermia was the only factor significantly correlated with serious toxicity. Conclusion : These results, a 93% total response with only 7% serious toxicity, are encouraging especially in the context of the patient population treated. Phase II/III studies involving ferromagnetic implantation are warranted.