Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas

BACKGROUND:

The authors report on the local control and toxicity of stereotactic body radiotherapy (SBRT) for patients with unresectable pancreatic adenocarcinoma.

METHODS:

Seventy‐seven patients with unresectable adenocarcinoma of the pancreas received 25 gray (Gy) in 1 fraction. Forty‐five patients (58%) had locally advanced disease, 11 patients (14%) had medically inoperable disease, 15 patients (19%) had metastatic disease, and 6 patients (8%) had locally recurrent disease. Nine patients (12%) had received prior chemoradiotherapy. Sixteen patients (21%) received between 45 to 54 Gy of fractionated radiotherapy and SBRT. Various gemcitabine‐based chemotherapy regimens were received by 74 patients (96%), but 3 patients (4%) did not receive chemotherapy until they had distant failure.

RESULTS:

The median follow‐up was 6 months (range, 3‐31 months) and, among surviving patients, it was 12 months (range, 3‐31 months). The overall rates of freedom from local progression (FFLP) at 6 months and 12 months were 91% and 84%, respectively. The 6‐ and 12‐month isolated local recurrence rates were 5% and 5%, respectively. There was no difference in the 12‐month FFLP rate based on tumor location (head/uncinate, 91% vs body/tail, 86%; P = .52). The progression‐free survival (PFS) rates at 6 months and 12 months were 26% and 9%, respectively. The PFS rate at 6 months was superior for patients who had nonmetastatic disease versus patients who had metastatic disease (28% vs 15%; P = .05). The overall survival (OS) rates at 6 months and 12 months from SBRT were 56% and 21%, respectively. Four patients (5%) experienced grade ≥2 acute toxicity. Three patients (4%) experienced grade 2 late toxicity, and 7 patients (9%) experienced grade ≥3 late toxicity. At 6 months and 12 months, the rates of grade ≥2 late toxicity were 11% and 25%, respectively.

CONCLUSIONS:

SBRT for pancreatic adenocarcinoma was effective for local control with associated risk of toxicity and should be used with rigorous attention to quality assurance. Efforts to reduce complications are warranted. Distant metastases account for the vast majority of disease‐related mortality. Cancer 2009. © 2008 American Cancer Society.     

Combination chemotherapy with S-1 plus cisplatin for gastric cancer that recurs after adjuvant chemotherapy with S-1: multi-institutional retrospective analysis

Background

It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy.

Methods

We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy.

Results

In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1?months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4?months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8?months, and the median overall survival (OS) was 12.2?months. Compared with patients with an RFI of <6?months (n?=?25), patients with an RFI of ≥6?months (n?=?27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2?months, respectively), and longer overall survival (7.3 vs. 16.6?months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6?months was still significantly associated with PFS and OS.

Conclusions

S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of ≥6?months.     

Cardiac Dose and Survival After Stereotactic Body Radiotherapy for Early-stage Non–Small-cell Lung Cancer

Introduction

Recent analyses have identified cardiac dose as an important predictor of overall survival (OS) after chemoradiation for locally advanced non–small-cell lung cancer (NSCLC). However, the survival influence of the cardiac dose after stereotactic body radiotherapy (SBRT) is unknown. We performed a dose–volume histogram (DVH) analysis of patients treated with SBRT for early stage NSCLC to examine survival and cardiac toxicity.

Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer

Background

While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described.

Methods

This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score.

Results

We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS.

Conclusions

These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.     

Adjuvant Systemic Therapy in Patients With Early-Stage NSCLC Treated With Stereotactic Body Radiation Therapy

Introduction

Stereotactic body radiation therapy (SBRT) is commonly used to treat nonsurgical patients with early-stage NSCLC. There are no prospective data on the role of adjuvant chemotherapy in this setting.

Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma

Background

Hepatocellular carcinoma (HCC) is increasing in incidence and the majority of patients are not candidates for radical therapies. Therefore, interest in minimally invasive therapies in growing.

Methods

A Phase I dose escalation trial was conducted at Indiana University to determine the feasibility and toxicity of stereotactic body radiation therapy (SBRT) for primary HCC. Eligible patients had Child-Turcotte-Pugh’s Class (CTP) A or B, were not candidates for resection, had 1–3 lesions and cumulative tumour diameter less than or equal to 6 cm. Dose escalation started at 36 Gy in 3 fractions (12 Gy/fraction) with a subsequent planned escalation of 2 Gy/fraction/level. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events v3.0 grade 3 or greater toxicity.

Results

Seventeen patients with 25 lesions were enrolled. Dose was escalated to 48 Gy (16 Gy/fraction) in CTP-A patients without DLT. Two patients with CPC-B disease developed grade 3 hepatic toxicity at the 42-Gy (14 Gy/fraction) level. The protocol was amended for subsequent CTP-B patients to receive a regimen of 5 fractions starting at 40 Gy (8 Gy/fraction) with one patient experiencing progressive liver failure. Four additional patients were enrolled (one died of unrelated causes after an incomplete SBRT course) without DLT. The only factor related to more than one grade 3 or greater liver toxicity or death within 6 months was the CTP score (p=0.03). Six patients underwent a liver transplant. Ten patients are alive without progression with a median FU of 24 months (10–42 months), with local control/stabilisation of the disease of 100%. One and two-year Kaplan-Meier estimates for overall survival are 75% and 60%, respectively.

Conclusions

SBRT is a non-invasive feasible and well tolerated therapy in adequately selected patients with HCC. The preliminary local control and survival are encouraging. A confirmatory Phase II trial is currently open to accrual.     

SBRT for Hepatocellular Carcinoma: 8-Year Experience from a Regional Transplant Center

Purpose

The study aimed to evaluate stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) in patients not eligible for liver transplant (LT).

Methods

We retrospectively identified transplant-ineligible HCC patients treated with SBRT to the liver between 2004 and 2013. Our primary endpoint was overall survival (OS). We also report treatment toxicities using CTCAE 3.0, radiographic response, and patterns of failure.

Results

We identified 93 patients with median age at SBRT of 65.8 years. Forty-six percent were classified as Child-Pugh B or C and 85% had an Eastern Cooperative Oncology Group performance status of 1–2. After SBRT, 86% of patients experienced no or mild treatment-related adverse events. Only 8% of patients experienced grade 3 and 2% of patients experienced grade 4 adverse events. Overall radiographic response was complete in 1.2%, partial in 35.4%, stable in 43.9%, and progressive disease in 19.5%. Median OS was 8.8 months with 1-, 2-, and 3-year OS rates of 38.0, 29.8 and 21.2%, respectively. The Cancer of the Liver Italian Program (CLIP) score was found to strongly correlate with survival. Median OS for patients with CLIP scores of 0, 1, 2, and 3 was 21.1, 8.5, 5.1, and 7.1 months, respectively (p = 0.003).

Conclusion

Our series demonstrates that SBRT is generally safe for HCC patients, even those with advanced liver failure. Although survival is generally poor, we were able to identify a group of patients with good liver function and early tumor stage who can achieve median OS of close to 2 years with SBRT.

     

The multimodal management of locally advanced N2 non-small cell lung cancer: is there a role for surgical resection? A single institution’s experience

Background

The management of operable locally advanced N2 non-small cell lung cancer (NSCLC) is a controversial topic. Concurrent chemoradiation (CT-RT) is considered the standard of care for inoperable or unresectable patients, but the role of trimodality treatment remains controversial. We present our institution??s experience with the management of stage III (N2) NSCLC patients, analyzing whether the addition of surgery improves survival when compared with definitive CT-RT alone.

Methods

From 1996 to 2006, 72 N2 NSCLC patients were treated. Thirty-four patients received cisplatin-based induction chemotherapy, followed by paclitaxel-cisplatin CT-RT, and 38 patients underwent surgery preceded by induction and/or followed by adjuvant therapy. Survival curves were estimated by Kaplan?CMeier analysis, and the differences were assessed with the log-rank test.

Results

Most of the patients (87?%) were men. The median age was 59?years. A statistically significant association between T3?CT4c and definitive CT-RT as well as between T1?CT2c and surgery was noted (p?<?0.0001). After a median follow-up period of 35?months, the median overall survival (OS) was 42?months for the surgery group versus 41?months for the CT-RT patients (p?=?0.590). The median progression-free survival (PFS) was 14?months after surgery and 25?months after CT-RT (p?=?0.933). Responders to radical CT-RT had a better OS than non-responders (43 vs. 17?months, respectively, p?=?0.011). No significant differences were found in the OS or PFS between the pN0 [14 (37.8?%) patients] and non-pN0 patients at thoracotomy. Three treatment-related deaths (7.8?%) were observed in the surgical cohort and none in the CT-RT group.

Conclusions

The addition of surgery did not render a median OS or PFS benefit when compared with CT-RT alone in our series of stage III-N2 NSCLC patients, in accordance with previously published data. However, responses to CT-RT had a greater impact in terms of OS and PFS. Although the patients selected for management including surgery showed a favorable T clinical staging in comparison to patients exclusively treated with definitive CT-RT, similar survival outcomes were found.     

Paclitaxel in combination with carboplatin as salvage treatment in patients with castration-resistant prostate cancer: a Hellenic oncology research group multicenter phase II study

Introduction

To evaluate the efficacy and tolerance of biweekly paclitaxel and carboplatin combination in patients with castration-resistant prostate cancer.

Patients and methods

Patients were treated with paclitaxel at the dose of 135?mg/m² followed by carboplatin AUC 3 on day 1 every 2?weeks in cycles of 28?days.

Results

Thirty-eight patients with castration-resistant prostate cancer were enrolled, and all of them had received frontline chemotherapy with docetaxel and prednisone, while 24 (63.2?%) had received 2 or more prior chemotherapy regimens. In an intention-to-treatment analysis, a clinical and/or biochemical response (>50?% decline) was observed in 10 patients (26.3?%; 95?% CI, 12.3?C40.3?%), stable disease in 13 (34.2?%) and progressive disease in 15 (39.5?%). The median duration of response was 6.1?months (range, 1.0?C9.8), the median time to tumor progression (TTP) 3.6?months (95?% CI, 2.1?C5.2) and the median overall survival 9.9?months (95?% CI, 6.2?C13.6). The probability for 1-year survival was 43?%. Grade 3 and 4 neutropenia was observed in three (7.9?%) and nine (23.7?%) patients, respectively.

Conclusion

The biweekly administration of paclitaxel/carboplatin regimen in patients with castration-resistant prostate cancer is an active and well-tolerated regimen which merits to be further evaluated in the context of salvage treatment.     

Fixed-dose-rate gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas

Background

Biliary tract cancers (BTC) have a poor prognosis, and there is no consensus on the best chemotherapy regimen. This study determined the response rate for fixed-dose-rate (FDR) gemcitabine combined with cisplatin.

Methods

This multicentre phase II trial enrolled 50 patients with inoperable locally advanced or metastatic BTC. Treatment consisted of FDR gemcitabine 1,000?mg/m² (10?mg/m²/min) and cisplatin 20?mg/m² on days 1 and 8 of a 21-day cycle. The primary endpoint was response rate. Secondary endpoints included safety, response duration (RD), progression-free (PFS) and overall survival (OS), and cancer antigen 19-9 response.

Results

Thirteen patients (26%, 95% CI 14.6?C40.4) had a partial response, and 12 (24%) had stable disease. The median RD was 8.3?months (95% CI 6.91?C9.99); median PFS 4?months (95% CI 2.5?C6.77); and median OS 6.8?months (95% CI 5.0?C8.7). Treatment was well tolerated. Grade 3 and grade 4 nausea, vomiting, and fatigue were uncommon. Thirty-eight per cent of patients discontinued treatment because of toxicity, patient or clinician preference.

Conclusions

This treatment combination had moderate activity with acceptable toxicity, supporting previous results that this combination has a role to play. The study does not suggest that FDR gemcitabine is superior to bolus infusion.     

Case Report: Long-Term Survival in Patients with Initial Lung-Only Metastasis from Pancreatic Adenocarcinoma

Purpose

Whilst surgery is the only potentially curative treatment for cholangiocarcinoma, many patients are either unfit for major surgery or have unresectable disease. Patients who undergo attempted curative resective surgery often have involved resection margins. The role of radiotherapy in these settings has not been clarified and is often not considered because of fears of late complications, especially liver and gastrointestinal toxicity. We present our experience of treating cholangiocarcinoma, either unresectable or locally advanced, with conformal radiotherapy and concurrent chemotherapy, examining survival, toxicity, patterns of failure and details of radiotherapy and chemotherapy administered.

Methods

Between 1995 and 2005, 20 patients, median age 60.5?years (range 45?C78?years) with cholangiocarcinoma received radical conformal radiotherapy (median dose 46?Gy in 1.8?C2.0?Gy fractions) with concurrent cisplatin/5-FU and sequential gemcitabine chemotherapy.

Results

Overall median survival was 20.4?months, 2?year survival, 43% and relapse-free survival, 9.6?months. 19/20 patients (95%) have died. One patient remains alive with liver and bone metastases. First site of failure was local and within radiotherapy field in 9/20 (45%) patients. No patient required interruption of radiotherapy for radiation toxicity, and none experienced subsequent late liver toxicity.

Conclusions

The survival of this group of historically poor prognosis patients is encouraging. Durable local control was achieved in a majority of patients having chemoradiotherapy and toxicity was not severe. Although most patients still succumbed to disease, treatment delayed onset of progression. Conformal radiotherapy should be considered as an integral component in new investigative approaches to treatment in this rare cancer.     

Phase II study of short-course capecitabine plus oxaliplatin (XELOX) followed by maintenance capecitabine in advanced colorectal cancer: XelQuali study

Purpose

To evaluate the efficacy, safety and quality of life of a short course of oxaliplatin plus capecitabine (XELOX) followed by single-agent capecitabine in patients with previously untreated, inoperable, metastatic colorectal cancer.

Methods

Patients received intravenous oxaliplatin 130?mg/m² on d1 plus oral capecitabine 1,000?mg/m² twice daily (bid) on d1?C14 every 21?days for four cycles. Patients achieving stable disease (SD) or better than received capecitabine 1,250?mg/m² bid on d1?C14 every 21?days until disease progression. The primary endpoint was progression-free survival (PFS).

Results

Overall, 21/45 (47%) of patients responded to the initial XELOX chemotherapy whilst SD or better was documented in 76%. Median PFS was 6.7 (95% CI 5.7?C9.6) months, and median overall survival (OS) was 20.5 (95% CI 13.1?C28.1) months. In the 34 patients who then received capecitabine maintenance therapy, the median PFS was 8.1 (95% CI 6.2?C11.8) months and median OS was 23.1 (95% CI 17.8?C28.5) months. A marked reduction in the vast majority of all grades of adverse event occurred on switching from initial XELOX to maintenance capecitabine chemotherapy including grades 1?C2 (77 vs. 47%) and grade 3 (7 vs. 3%) neuropathy, diarrhoea and lethargy.

Conclusions

Short-course XELOX followed by capecitabine maintenance therapy provides an active and well-tolerated treatment option for patients with previously untreated metastatic colorectal cancer. A median OS of more than 20?months is promising and by limiting the number of oxaliplatin infusions, this approach minimises the risk of unwanted cumulative neurotoxicity, is cheaper and more convenient for both patients and healthcare providers.     

Combination of peptide receptor radionuclide therapy with fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma

Background

The purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB).

Methods and materials

We evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60?Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60?Gy); in-field (recurrence in the high-dose volume of 50?Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field).

Results

The median follow-up durations were 13?months for all patients and 19?months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20?months for AA patients and 15?months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P?=?0.014), while the extent of surgical removal (P?=?0.47) and regimens of chemotherapy (P?=?0.57) did not.

Conclusions

MIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease.     

Safety of adjuvant trastuzumab for HER-2-overexpressing elderly breast cancer patients: a multicenter cohort study

Background

For targeting anti-HER-2, trastuzumab-incorporated chemotherapy is the standard for HER-2-overexpressing breast cancer in adjuvant settings. But there are few data on trastuzumab in elderly patients. We evaluated the incidence of adverse events among an elderly population of trastuzumab-treated HER-2-positive breast cancer patients in adjuvant settings.

Methods

Data on 39 elderly HER-2 overexpressing breast cancer patients treated with both curative surgery and adjuvant trastuzumab were retrospectively collected from a Japanese multicenter study. The loading dose was 8?mg/kg body weight, and the maintenance dose was 6?mg/kg every 3?weeks; or the loading dose was 4?mg/kg followed by 2?mg/kg weekly as maintenance.

Results

After a median follow-up of 20.0?(2.4?C53.9)?months, a total of 32 patients (82.1%) completed 1-year trastuzumab treatment. The median treatment duration was 12.0?months (range 2?C12; mean 10.5). Adverse events occurred in 11 patients (28.2%). Four (10.2%) discontinued or interrupted treatment after experiencing toxicity. One patient died because of interstitial pneumonia. Three patients (7.7%) had congestive heart failure (CHF), one of whom had a history of angina. Three patients (7.7%) had a lower left ventricular ejection fraction (LVEF), and brain natriuretic peptide elevation was totally observed in three patients (7.7%). Three patients with lower LVEF had received chemotherapy containing doxorubicin before trastuzumab. Of the three patients, two discontinued therapy because of CHF, but all recovered with proper medication containing a diuretic agent.

Conclusions

Elderly patients tolerated trastuzumab well, although careful management is needed.     

A phase II study of docetaxel and oxaliplatin combination in recurrent gastric cancer patients after fluoropyrimidine and/or cisplatin adjuvant treatment: a Korean Cancer Study Group Protocol ST06-02

Background

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.

Methods

Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35?mg/m²) intravenously on day 1 and 8 plus oxaliplatin (100?mg/m²) intravenously on day 1 every 3?weeks until disease progression or unacceptable toxicity.

Results

A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6?months (range, 1–48?months) were enrolled in this trial; 22 (64.7?%) patients had been exposed to both agents. Their median age was 58?years (range, 50–68?years). The overall response rate was 55.9?% (95?% confidence interval (CI), 38.3–73.5?%), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5?months (range, 9.2–50.7?months), the median progression-free survival for all patients was 5.3?months (95?% CI, 4.4–6.1?months) and the median overall survival was 13.8?months (95?% CI, 11.1–16.4?months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1?%) and diarrhea (17.6?%), respectively. Five patients (14.7?%) experienced febrile neutropenia.

Conclusions

Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.     

Adjuvant sequential chemoradiation therapy in high-risk endometrial cancer: results of a prospective, multicenter phase-II study of the NOGGO (North-Eastern German Society of Gynaecological Oncology)

Purpose

The management of high-risk endometrial cancer (HREC) remains controversial. We conducted a prospective multicenter phase-II clinical trial to evaluate an adjuvant chemotherapy (CT) with sequential radiotherapy (RT) in patients with HREC.

Methods

Patients with HREC from 8 institutions in Germany were enrolled. After surgery, patients received four cycles of paclitaxel 175 mg/m² (P) and carboplatin AUC5 (C) (d1, q21d) and subsequent external pelvic radiation therapy (1.8 Gy/d, d1-5) at a total dose of 45 Gy with vaginal brachytherapy (3 × 5 Gy). Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire. Primary endpoints were tolerability, toxicity and QoL. Progression-free survival (PFS) was defined as secondary endpoint.

Results

Thirty-five patients were enrolled from 2004 through 2008. Median follow-up was 24 months (range 3–24 months). All patients received 4 cycles of P and C and completed RT. Overall, grade 3/4 haematological toxicity was 25.6 %. Three cycles were delayed because of leukopenia. Grade 3/4 non-haematologic toxicities were rare (≤3 %). No overall change in QoL occurred during treatment. Two-year median PFS and OS rates were both 75.8 %.

Conclusions

Adjuvant combination CT with P + C and sequential RT is well tolerated and a feasible regimen in patients with HREC. Subsequent phase-III trials are warranted.     

Adjuvant postoperative radiochemotherapy for patients with gastric carcinoma: a single institution experience

Objective

The suboptimal outcome after surgery alone for gastric cancer indicated the necessity of adjuvant treatment for potentially resectable carcinoma of the stomach. In 2001, postoperative adjuvant radiochemotherapy started to be implemented in the NCI, Cairo, Egypt. However, the fear of the acute complication hindered its use as a standard treatment with some staff didn’t follow the SWAG’s adjuvant protocol. The aim of this report is to verify this issue.

Methods

In the period from 1999 to 2009, 320 out of 581 patients with gastric carcinoma, underdid potentially curative surgery. Adjuvant postoperative radiochemotherapy for stage ≥ IIA started since 2001. Radiation (45 Gy, 1.8 Gy/f) was targeted to the tumor bed, anastomosis site, duodenal stump, remnant stomach and regional lymph node together with 4–5 cycles chemotherapy (SWOG protocol). Survival analysis was performed and comparison between survival curves was done to analysis different prognostic factors.

Results

The patients’ age ranged from 17 to 86 years [mean (54 ± 12.5) years]. About 1/3 of the patients had a diffuse lesion. Adenocarcinoma was the most common pathology (60.4%). High grade pathology constituted 59.1% of the cases. About one fifth of the patients had metastatic disease at presentation. Only 351 (75%) of the patients had potentially curative gastrectomy. The median number of lymph node (LN) dissected was 12 (ranged from 0–45) with a median number of the positive LN of 3.5 (ranged from 0–40). Postoperative mortality was 12%. The median follow up period was 21.9 months (ranged from 3–129.4 months). For the 257 patients who had curative surgery, 164 (62.8%) patients were alive at the end of follow up. During follow up period, 30 patients had loco-regional relapse, and 26 patients had metastasis, and 39 patients had both pattern of failure. The overall survival (OS), loco-regional control (LRC), and metastasis free survival (MFS) rates, at median follow up period of 22 months, were 61.2%, 66.7% and 71%, respectively. At 3 and 5 years the corresponding values were: OS (42% and 28%), LRC (64% and 50.4%) and MFS (56.3% and 49%), respectively. Only stage and degree of nodal involvement had an adverse effect on all survival rates. Proximal lesion had poor OS rates. As regard LR control rate, mucinous cell type, and high grade had a bad effect. Although patients with less than D1 dissection had low OS and LRC rate, it didn’t reach significant level. There was a significant improved 5-year OS rate for concurrent chemoradiotherapy (CCRTh, 55%) versus no or single adjuvant modality (27%), P = 0.035. A subgroup analysis according to CTH regimen showed a trend for all survival rates with ECF compared to bolus 5FU/LV. However, none was statistically significant.

Conclusion

In operable gastric carcinoma, postoperative concomitant radiochemotherapy with 5FU and LV is feasible with acceptable toxicity with a significant increase of locoregional control. A well designed phase III clinical trial — with ECF regimen and conformal radiotherapy — is worth to start to increase local control and decrease toxicity.     

Scoring system predictive of survival for patients undergoing stereotactic body radiation therapy for liver tumors

ABSTRACT: BACKGROUND: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumors. This study evaluated outcomes after SBRT to identify prognostic variables and to develop a novel scoring system predictive of survival. METHODS: The medical records of 52 patients with a total of 85 liver lesions treated with SBRT from 2003 to 2010 were retrospectively reviewed. Twenty-four patients had 1 lesion; 27 had 2 or more. Thirteen lesions were primary tumors; 72 were metastases. Fiducials were placed in all patients prior to SBRT. The median prescribed dose was 30 Gy (range, 16 -- 50 Gy) in a median of 3 fractions (range, 1--5). RESULTS: With median follow-up of 11.3 months, median overall survival (OS) was 12.5 months, and 1 year OS was 50.8%. In 42 patients with radiographic follow up, 1 year local control was 74.8%. On univariate analysis, number of lesions (p = 0.0243) and active extralesional disease (p < 0.0001) were predictive of OS; Karnofsky Performance Status (KPS) approached statistical significance (p = 0.0606). A scoring system for predicting survival was developed by allocating 1 point for each of the three following factors: active extralesional disease, 2 or more lesions, and KPS <= 80%. Score was associated with OS (p < 0.0001). For scores of 0, 1, 2 and 3, median survival intervals were 34, 12.5, 7.6, and 2.8 months, respectively. CONCLUSIONS: SBRT offers a safe and feasible treatment option for liver tumors. A prognostic scoring system based on the number of liver lesions, activity of extralesional disease, and KPS predicts survival following SBRT and can be used as a guide for prospective validation and ultimately for treatment decision-making.     

Safety and Feasibility of Carboplatin and Paclitaxel followed by Fluoropyrimidine Analogs and Radiation as Adjuvant Therapy for Gastric Cancer

Background

Adjuvant 5-fluorouracil (5FU)-based chemo-radiotherapy is currently considered a standard of care for the treatment of gastric cancer. The impact of 5FU-based adjuvant therapy on the rate of distant recurrence has been modest. In order to improve the systemic effects of adjuvant therapy, we have been treating patients with resected gastric cancer with carboplatin and paclitaxel followed by fluoropyrimidine analogue and radiation.

Methods

We report on the outcomes of 21 consecutive gastric cancer patients treated off protocol with adjuvant carboplatin (area under the curve 5 mg/ml × min) and paclitaxel (175–200 mg/m²) every 3 weeks, followed by concurrent pyrimidine analogs (either capecitabine 1,600–2,000 mg/m²/day in 17 patients, or 5FU 200 mg/m²/day in 4 patients) and radiation (45–50.4 Gy). Patients received a total of 4–6 cycles of carboplatin and paclitaxel.

Results

The median age at diagnosis was 60 years. Sixteen patients had stage 3 disease and 7 of them had positive surgical margins (6 with R1 and 1 with R2 resection), 3 patients were stage 2, and 2 patients were stage 1 (all had R0 resection). All patients had D1/D2 (4 had D2 and 17 had D1) lymph node dissection. The incidence of grade 3 or higher overall, hematologic, or gastrointestinal toxicity in the patients receiving carboplatin and paclitaxel was 57, 48 and 10%, respectively. No treatment-related deaths were observed. After adjuvant treatment 15 patients developed recurrent disease, 10 of whom had distant metastases. The median recurrence-free survival (RFS) was 12.3 months. The median overall survival (OS) was 16.0 months. Patients with R0 resection had significantly longer OS than did those with positive surgical margins (log-rank p = 0.0060). Median OS for the R0 resection group was 28.8 months.

Conclusions

Carboplatin and paclitaxel added to radiation plus fluoropyrimidine analogs is a well-tolerated regimen in the adjuvant setting. The activity of this regimen in this relatively high-risk group of gastric cancer patients is of interest for future development.Key Words: Paclitaxel, Carboplatin, Adjuvant, Gastric, Radiation     

Thoracic re-irradiation using stereotactic body radiotherapy (SBRT) techniques as first or second course of treatment

Background and purpose

Management for in-field failures after thoracic radiation is poorly defined. We evaluated SBRT as an initial or second course of treatment re-irradiating in a prior high dose region.

Materials and methods

Thirty-three patients were treated with re-irradiation defined by the prior 30 Gy isodose line. Kaplan–Meier estimates were performed for local (LC), regional (RC), distant control (DC), and overall survival (OS). The plans when available were summed to evaluate doses to critical structures. Patient and treatment variables were analyzed on UVA for the impact on control and survival measures.

Results

Median follow-up was 17 months. Treatment for sequential courses was as follows: (course1:course2) EBRT:SBRT (24 patients), SBRT:SBRT (7 patients), and SBRT:EBRT (3 patients). Median re-irradiation dose and fractionation was 50 Gy and 10 fractions (fx), with a median of 18 months (6–61) between treatments. Median OS was 21 months and 2 year LC 67%, yet LC for >1 fraction was 88% (p = 0.006 for single vs. multiple). 10 patients suffered chronic grade 2–3 toxicity (6 chest wall pain, 3 dyspnea, 1 esophagitis) and 1 grade 5 toxicity with aorta-esophageal fistula after 54 Gy in 3 fx for a central tumor with an estimated EQD2 to the aorta of 200 Gy.

Conclusion

Tumor control can be established with re-irradiation using SBRT techniques for in-field thoracic failures at the cost of manageable toxicity.