Radiation therapy target volume reduction in pediatric rhabdomyosarcoma

BACKGROUND:

The use of radiation therapy (RT) “cone‐down” boost to reduce high‐dose treatment volumes according to tumor response to induction chemotherapy in patients with pediatric rhabdomyosarcoma (RMS) may reduce treatment morbidity, yet the impact on tumor control is unknown.

METHODS:

Fifty‐five children, including 18 (33%) with parameningeal (PM) RMS and 37 (67%) with non‐PM RMS, who received definitive treatment with chemotherapy and RT from April 2000 through January 2010 were retrospectively reviewed.

RESULTS:

In total, 28 patients (51%) received a cone‐down boost. The high‐dose boost volume was reduced by a median of 56% of the initial target volume (range, 5%‐91%). The median time to initiating RT was 3 weeks for patients with PM RMS and 16 weeks for patients with non‐PM RMS (P < .001). After a median follow‐up of 41 months, local failure occurred in 5 patients (9%), including 2 patients who received a cone‐down boost, and there were no marginal failures. Twelve patients (67%) with PM RMS had intracranial tumor extension. In this subgroup, 4 patients (30%) who received a cone‐down boost and had ≥ 3 weeks between chemotherapy and RT initiation experienced leptomeningeal failure as their first site of disease progression, and a delayed time to RT initiation was associated with decreased survival (P = .055)

CONCLUSIONS:

A cone‐down boost allowed for significant reductions in high‐dose RT treatment volume while maintaining excellent tumor control in most patients. However, in the subset of patients with PM RMS and intracranial tumor extension, early RT initiation and wider margin RT to cover adjacent areas at high risk for meningeal extension may be more important for adequate disease control. Cancer 2013. © 2012 American Cancer Society.     

The role of technetium‐99m methoxyisobutyl isonitrile scintigraphy in predicting the therapeutic effect of chemotherapy against nasopharyngeal carcinoma

BACKGROUND:

The authors prospectively evaluated the correlation between technetium‐99m methoxyisobutyl isonitrile (^99mTc‐MIBI) accumulation in tumors and response to induction chemotherapy in patients with nasopharyngeal carcinoma (NPC).

METHODS:

Eighty‐six patients with locally advanced NPC underwent single‐photon emission computed tomography 15 minutes after an intravenous injection of 740 megabecquerels (20 mCi) ^99mTc‐MIBI before chemotherapy. The tumor uptake ratio (TUR) was calculated. Two weeks after the second cycle of combined chemotherapy with 5‐fluorouracil (5‐FU) and cisplatin (DDP), the tumor response rate was evaluated. The correlation between ^99mTc‐MIBI accumulation in tumors and response to chemotherapy with 5‐FU/DDP was examined.

RESULTS:

Positive accumulation of ^99mTc‐MIBI in tumors was observed in 76 patients (88.4%). The tumor response was a complete response (CR) in 8 patients, a partial response (PR) in 68 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. The response rate (CR and PR) to 5‐FU/DDP chemotherapy in patients who had positive ^99mTc‐MIBI accumulation (tumor uptake ratio [TUR] >1.1) was higher than that in patients who had negative ^99mTc‐MIBI accumulation (TUR ≤1.1; 98.7% vs 10%; P < .001).

CONCLUSIONS:

Patients with negative ^99mTc‐MIBI accumulation were resistant to 5‐FU/DDP chemotherapy. ^99mTc‐MIBI imaging in patients with NPC was capable of predicting tumor response to chemotherapy with 5‐FU/DDP and can help in the selection of patients for induction chemotherapy. Cancer 2011. © 2010 American Cancer Society.     

Platin‐based exclusive chemotherapy for selected patients with squamous cell carcinoma of the larynx and pharynx

BACKGROUND:

The current study was conducted to determine the long‐term outcomes of patients with squamous cell carcinoma of the larynx and pharynx who were treated with platin‐based exclusive chemotherapy (EC) after they achieved a complete clinical response (CCR) to induction chemotherapy.

METHODS:

One hundred forty‐two who achieved a CCR after platin‐based induction chemotherapy were treated exclusively with additional chemotherapy, and 98.6% were followed for a minimum of 3 years or until death. Thirty‐five patients had >10 years of follow‐up.

RESULTS:

The survival rates at 1 year and 5 years were 95.8% and 61.2%, respectively. The main causes of death were metachronous second primary tumors (n = 27) and intercurrent disease (n = 21). Death related to EC was not encountered, and only 2 patients (1.4%) had grade 4 toxicity. In multivariate analysis, primary tumor arising outside the glottic larynx (P = .0001) and a Charlson comorbidity index >1 (P = .0001) were associated with a statistically significant reduction in survival. The 1‐year and 5‐year Kaplan‐Meier local control estimates were 76.1% and 50.7%, respectively. Salvage treatment resulted in an observed final local control rate of 93% that varied from 97.2% in patients who had glottic cancer to 88.7% in patients who had tumor originating from other sites (P = .097). Combined chemotherapy with cisplatin and 5‐fluorouracil (PF) allowed for the successful modulation of local therapy in 54.9% of patients.

CONCLUSIONS:

For selected patients, EC may provide long‐term, durable disease control. For patients who developed recurrent disease after EC, this approach did not diminish survival and maintained function in the majority of patients. Future work should be directed toward select markers of response to PF chemotherapy with which to identify those patients who are suited optimally for this approach. Cancer 2009. © 2009 American Cancer Society.     

Clinical benefits of systemic chemotherapy for patients with metastatic pheochromocytomas or sympathetic extra-adrenal paragangliomas: insights from the largest single-institutional experience

BACKGROUND:

The objective of this study was to evaluate the clinical benefits of systemic chemotherapy for patients with metastatic pheochromocytomas or sympathetic paragangliomas by assessing reductions in tumor size and blood pressure and improvements in overall survival (OS).

METHODS:

The authors retrospectively reviewed the medical records of patients with metastatic pheochromocytomas‐sympathetic paragangliomas who had received chemotherapy at The University of Texas MD Anderson Cancer Center.

RESULTS:

Clinical benefit and OS were assessed. Of 54 patients who received chemotherapy, 52 patients were evaluable for response. Seventeen patients (33%) experienced a response, which was defined as decreased or normalized blood pressure/decreased number and dosage of antihypertensive medications and/or reduced tumor size after the first chemotherapy regimen. The median OS was 6.4 years (95% confidence interval [CI], 5.2‐16.4 years) for responders and 3.7 years (95% CI, 3.0‐7.5 years) for nonresponders. Among the patients who had synchronous metastatic disease, a positive response at 1 year after the start of chemotherapy was associated with a trend toward longer OS (log‐rank test; P = .095). In a multivariate Cox proportional hazards model, the effect of response to chemotherapy on OS was significant (hazard ratio, 0.22; 95% CI, interval: 0.05‐1.0; P = .05). All responders had received dacarbazine and cyclophosphamide. Vincristine was included for 14 responders, and doxorubicin was included for 12 responders. The clinical factors that predicted response to chemotherapy could not be identified.

CONCLUSIONS:

The current results indicted that chemotherapy may decrease tumor size and facilitate blood pressure control in approximately 33% of patients with metastatic pheochromocytoma‐sympathetic paraganglioma. These patients exhibited longer survival. Cancer 2011. © 2011 American Cancer Society.     

Hormone-receptor expression and activity of trastuzumab with chemotherapy in HER2-positive advanced breast cancer patients

BACKGROUND:

The relationship between quantitative immunohistochemical hormone receptor expression and response to the combination of trastuzumab with chemotherapy in HER2‐positive advanced breast cancer is currently unknown.

METHODS:

Estrogen receptor (ER) and progesterone receptor expression was studied both as a dichotomous variable (positivity set at ≥1% of positive cells) and as a continuous variable. The effect of hormone receptor expression on overall response rate and progression‐free survival in patients receiving trastuzumab‐based treatment was studied by univariate and multivariate analysis.

RESULTS:

One hundred eleven of 227 consecutive advanced breast cancer patients treated at 2 Institutions had hormone receptor‐positive tumors (49%). High expression of ER (≥30% of tumor cells) predicted reduced probability of tumor response to trastuzumab plus chemotherapy (multivariate odds ratio, 0.422; 95% confidence interval [CI], 0.222‐0.803; P = .009). In patients with hormone receptor‐positive tumors (≥1% of tumor cells), maintenance endocrine therapy added to trastuzumab upon the completion of chemotherapy was associated with a significant progression‐free survival benefit (hazard ratio, 0.521; 95% CI, 0.3325‐0.836; P = .007).

CONCLUSIONS:

Our results suggest a predictive role of hormone receptor expression in HER2‐positive tumors. Further investigation in this patient subset is warranted to optimize the use of HER2‐targeting agents, chemotherapy, and endocrine therapy. Cancer 2012;. © 2011 American Cancer Society.     

A novel therapeutic combination for neuroblastoma

BACKGROUND:

High‐risk cases of neuroblastoma have poor survival rates, and novel therapies are needed. Vandetanib (ZD6474, Zactima) is an inhibitor of the vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases, which have each been implicated in neuroblastoma pathogenesis. The authors hypothesized that vandetanib combined with 13‐cis‐retinoic acid (CRA), a differentiating agent used in most current neuroblastoma treatment regimens, would be effective against neuroblastoma tumor models.

METHODS:

The authors evaluated the effects of vandetanib with and without CRA on RET phosphorylation and on the proliferation and survival of human neuroblastoma cell lines in vitro. Using a subcutaneous mouse xenograft model of human neuroblastoma, they analyzed tumors treated with CRA, vandetanib, and the combination of vandetanib plus CRA for growth, gross and histologic appearance, vascularity, and apoptosis.

RESULTS:

Vandetanib treatment inhibited RET phosphorylation and resulted in induction of apoptosis in the majority of neuroblastoma cell lines in vitro, whereas CRA treatment induced morphologic differentiation and cell‐cycle arrest. Treatment with vandetanib plus CRA resulted in more significant reduction in neuroblastoma cell viability than either alone. In a mouse xenograft model, the combination of vandetanib with CRA demonstrated significantly more growth inhibition than either alone, via both reduction in tumor vascularity and induction of apoptosis.

CONCLUSIONS:

Vandetanib induces neuroblastoma tumor cell death in vitro and reduces tumor growth and vascularity in vivo. The combination of vandetanib with CRA was more effective in reducing tumor growth than either treatment alone. The antitumor effects of vandetanib plus CRA suggest a novel combination for use in neuroblastoma patients. Cancer 2010. © 2010 American Cancer Society.     

Ultra‐early predictive assay for treatment failure using functional magnetic resonance imaging and clinical prognostic parameters in cervical cancer

BACKGROUND:

The authors prospectively evaluated magnetic resonance imaging (MRI) parameters quantifying heterogeneous perfusion pattern and residual tumor volume early during treatment in cervical cancer, and compared their predictive power for primary tumor recurrence and cancer death with the standard clinical prognostic factors. A novel approach of augmenting the predictive power of clinical prognostic factors with MRI parameters was assessed.

METHODS:

Sixty‐two cervical cancer patients underwent dynamic contrast‐enhanced (DCE) MRI before and during early radiation/chemotherapy (2‐2.5 weeks into treatment). Heterogeneous tumor perfusion was analyzed by signal intensity (SI) of each tumor voxel. Poorly perfused tumor regions were quantified as lower 10th percentile of SI (SI[10%]). DCE‐MRI and 3‐dimensional (3D) tumor volumetry MRI parameters were assessed as predictors of recurrence and cancer death (median follow‐up, 4.1 years). Their discriminating capacity was compared with clinical prognostic factors (stage, lymph node status, histology) using sensitivity/specificity and Cox regression analysis.

RESULTS:

SI(10%) and 3D volume 2‐2.5 weeks into therapy independently predicted disease recurrence (hazard ratio [HR], 2.6; 95% confidence interval [95% CI], 1.0‐6.5 [P = .04] and HR, 1.9; 95% CI, 1.1‐3.5 [P = .03], respectively) and death (HR, 1.9; 95% CI, 1.0‐3.5 [P = .03] and HR, 1.9; 95% CI, 1.2‐2.9 [P = .01], respectively), and were superior to clinical prognostic factors. The addition of MRI parameters to clinical prognostic factors increased sensitivity and specificity of clinical prognostic factors from 71% and 51%, respectively, to 100% and 71%, respectively, for predicting recurrence, and from 79% and 54%, respectively, to 93% and 60%, respectively, for predicting death.

CONCLUSIONS:

MRI parameters reflecting heterogeneous tumor perfusion and subtle tumor volume change early during radiation/chemotherapy are independent and better predictors of tumor recurrence and death than clinical prognostic factors. The combination of clinical prognostic factors and MRI parameters further improves early prediction of treatment failure and may enable a window of opportunity to alter treatment strategy. Cancer 2010. © 2010 American Cancer Society.     

Early clearance of peripheral blood blasts predicts response to induction chemotherapy in acute myeloid leukemia

BACKGROUND:

Early marrow blast clearance 14 days after induction chemotherapy is an independent prognostic indicator of outcomes in acute myeloid leukemia (AML).

METHODS:

We evaluated the relationship between time to peripheral blood blast clearance after induction and disease status as assessed by day 14 and day 30 marrow biopsies in 162 patients with AML. Day 6 after induction was the optimal cutoff point determined by a receiver operating characteristic analysis and was selected to divide patients into early blast clearance (EBC; ≤6 days; n = 119) and delayed blast clearance (DBC; >6 days; n = 43) groups.

RESULTS:

DBC patients were older, but otherwise the 2 groups were comparable. Marrow blast clearance on day 14 after induction chemotherapy was observed in 84% of patients in the EBC group and 60% in the DBC group. With a median follow‐up of 1538 days, both relapse‐free survival (RFS) (442 vs 202 days, P = .0017) and overall survival (OS) (930 vs 429 days, P < .0001) were longer in the EBC group, and a multivariable analysis showed that EBC independently predicted clearance of marrow blasts at day 14 (P = .0018), remission (P = .0179), RFS (P = .0171), and OS (P = .0122).

CONCLUSIONS:

Early clearance of peripheral blood blasts after induction chemotherapy predicts for early marrow blast clearance, complete remission, RFS, and OS. Cancer 2012. © 2012 American Cancer Society.     

Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases

BACKGROUND.

The current study evaluated the effect of bevacizumab added to fluoropyrimidine‐plus‐oxaliplatin (5FU/OX) chemotherapy for colorectal liver metastases (CLM) on the pathologic response and nontumorous liver histology.

METHODS.

A total of 105 consecutive patients treated preoperatively with 5FU/OX chemotherapy with (n = 62) or without (n = 43) bevacizumab were analyzed. The response to chemotherapy was evaluated by pathologic analysis of tumor viability (percentage of viable tumor in relation to tumor surface area). The incidence and grade of hepatic sinusoidal dilation were also investigated.

RESULTS.

Bevacizumab‐containing regimens significantly reduced the degree of tumor viability compared with 5FU/OX‐only chemotherapy (32.9% vs 45.3%; P = .02). After stratification according to the magnitude of tumor viability, a higher proportion of patients treated with bevacizumab than without had <25% residual viable tumor cells (45% vs 23%; P = .02). However, the addition of bevacizumab to 5FU/OX did not appear to increase the incidence of complete pathologic response (11.3% vs 11.6%; P = .59). The incidence and severity of sinusoidal dilation was lower in patients treated with bevacizumab than in those treated with 5FU/OX only (any grade: 27.4% vs 53.5%; moderate or severe: 8.1% vs 27.9%; both P < .01).

CONCLUSIONS.

In patients treated with 5FU/OX chemotherapy, bevacizumab improves the pathologic response, as demonstrated by a reduction of the degree of tumor viability, and reduces the incidence and severity of hepatic injury. This retrospective study provides additional evidence supporting the use of bevacizumab in combination with 5FU/OX for CLM. Cancer 2007. © 2007 American Cancer Society.     

Impact of post-therapy positron emission tomography on prognostic stratification and surveillance after chemoradiotherapy for cervical cancer

BACKGROUND:

A study was undertaken to investigate the detection of relapse and survival outcomes in patients with cervical cancer treated with curative intent chemoradiotherapy, and evaluated with a post‐therapy ¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scan.

METHODS:

Between January 2002 and June 2007, 105 consecutive patients were prospectively enrolled into a registry study designed to assess outcomes of chemoradiotherapy. A FDG‐PET scan was performed between 3 and 12 months (median, 4.9 months) post‐treatment at clinician discretion. Tumor response was graded as complete metabolic response, partial metabolic response, or progressive metabolic disease.

RESULTS:

Median follow‐up was 36 months. At post‐therapy FDG‐PET, 73 (70%) patients had complete metabolic response, 10 (9%) had partial metabolic response, and 22 (21%) had progressive metabolic disease. Overall survival at 3 years was 77% in all patients, and 95% for those with complete metabolic response. On multivariate analysis, complete metabolic response (P < .0001) and pretreatment tumor volume (P = .041) were strong predictors for overall survival. The number of involved lymph nodes (P < .005) and International Federation of Gynecology and Obstetrics stage (P = .04) were predictive of relapse‐free survival. In total, 18 patients relapsed at a single site, and 13 underwent salvage, with a 3‐year survival of 67%. Patients with complete metabolic response had a distant failure rate 36‐fold less than those with partial metabolic response (P < .0001). After complete metabolic response, only 1 patient (1.6%) relapsed without symptoms and was detected through physical examination.

CONCLUSIONS:

The presence of a complete metabolic response at post‐therapy FDG‐PET is a powerful predictor for survival after chemoradiation. The very low rate of recurrence in patients with a complete metabolic response justifies a conservative follow‐up approach for these patients, because relapse is usually symptomatic and not detected by routine clinical review. Cancer 2011. © 2011 American Cancer Society.     

UBE4B levels are correlated with clinical outcomes in neuroblastoma patients and with altered neuroblastoma cell proliferation and sensitivity to epidermal growth factor receptor inhibitors

BACKGROUND:

The UBE4B gene, which is located on chromosome 1p36, encodes a ubiquitin ligase that interacts with hepatocyte growth factor‐regulated tyrosine kinase substrate (Hrs), a protein involved in epidermal growth factor receptor (EGFR) trafficking, suggesting a link between EGFR trafficking and neuroblastoma pathogenesis. The authors analyzed the roles of UBE4B in the outcomes of patients with neuroblastoma and in neuroblastoma tumor cell proliferation, EGFR trafficking, and response to EGFR inhibition.

METHODS:

The association between UBE4B expression and the survival of patients with neuroblastoma was examined using available microarray data sets. UBE4B and EGFR protein levels were measured in patient tumor samples, EGFR degradation rates were measured in neuroblastoma cell lines, and the effects of UBE4B on neuroblastoma tumor cell growth were analyzed. The effects of the EGFR inhibitor cetuximab were examined in neuroblastoma cells that expressed wild‐type and mutant UBE4B.

RESULTS:

Low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma. UBE4B overexpression reduced neuroblastoma tumor cell proliferation, and UBE4B expression was inversely related to EGFR expression in tumor samples. EGFR degradation rates correlated with cellular UBE4B levels. Enhanced expression of catalytically active UBE4B resulted in reduced sensitivity to EGFR inhibition.

CONCLUSIONS:

The current study demonstrates associations between UBE4B expression and the outcomes of patients with neuroblastoma and between UBE4B and EGFR expression in neuroblastoma tumor samples. Moreover, levels of UBE4B influence neuroblastoma tumor cell proliferation, EGFR degradation, and response to EGFR inhibition. These results suggest UBE4B‐mediated growth factor receptor trafficking may contribute to the poor prognosis of patients who have neuroblastoma tumors with 1p36 deletions and that UBE4B expression may be a marker that can predict responses of neuroblastoma tumors to treatment. Cancer 2013. © 2012 American Cancer Society.     

Management of adult patients with acute lymphoblastic leukemia in first complete remission

BACKGROUND:

The optimal postremission therapy in adults with acute lymphoblastic leukemia (ALL) is still a matter of debate. The objective of this study was to compare the various potential therapeutic options for patients who achieved first complete remission.

METHODS:

The authors conducted a systematic review and meta‐analysis of randomized trials, including patients with standard‐risk (SR) All and high‐risk (HR) ALL who received first postremission therapy. Outcomes assessed were all‐cause mortality (ACM), disease recurrence (relapse), and nonrelapse mortality (NRM). Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled.

RESULTS:

Overall, there was a significant reduction in ACM in the allogenic stem cell transplantation (alloSCT) arm (RR, 0.88; 95% CI, 0.8‐0.97) compared with autologous stem cell transplantation (ASCT) or chemotherapy. Subgroup analyses revealed a similar pattern among SR patients (RR, 0.8; 95% CI, 0.68‐0.94) but a nonsignificant advantage for alloSCT among HR patients (RR, 0.88; 95% CI, 0.76‐1.01). There was an increase in NRM (RR, 2.99; 95% CI, 1.37‐6.53) and a decrease in the relapse rate in the alloSCT arm (RR, 0.52; 95% CI, 0.33‐0.83). There was no difference in ACM or the relapse rate between the ASCT and chemotherapy arms.

CONCLUSIONS:

Overall, alloSCT was superior to ASCT or chemotherapy for patients with ALL in first complete remission. The survival advantage was of greater statistical significance for patients with SR ALL than for patients with HR ALL. Cancer 2010. © 2010 American Cancer Society.     

Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy

BACKGROUND:

In neoadjuvant chemotherapy for advanced esophageal cancers, complete tumor regression has been difficult to achieve, and tumor often remained after chemotherapy. However, the best method for evaluating the response to chemotherapy based on histopathologic examination of residual tumors has not been established.

METHODS:

Studied were 74 patients who received neoadjuvant chemotherapy (5‐fluorouracil, cisplatin, and doxorubicin), followed by surgery for advanced esophageal squamous cell carcinoma. The correlation between various histopathologic factors and clinical response with survival was examined, including the importance of tumor budding in the invasive front of tumors on clinical response and survival.

RESULTS:

Among 74 patients, 3 achieved a pathologic complete response, and 29 (41%) of 71 residual tumors demonstrated high‐grade budding in the invasive front. The 5‐year survival rate of patients with low‐grade budding tumors was 49%, compared with 17% for those with high‐grade budding (P < .001). Budding correlated inversely with good response, which was observed in 44 (60%) of 74 patients. Univariate analysis showed that pathologic tumor depth, number of lymph node metastases, pathologic stage, lymphatic invasion, budding and clinical response were significant prognostic factors. Multivariate analysis identified budding as the most important prognostic factor followed by number of lymph node metastases.

CONCLUSIONS:

The results of the current study indicated that tumor budding in the invasive front of tumors correlated significantly with clinical response and prognosis of patients with esophageal squamous cell carcinomas who received neoadjuvant chemotherapy. However, the mechanism of tumor budding in the invasion front of esophageal squamous cell carcinomas treated with chemotherapy was not clarified. Cancer 2009. © 2009 American Cancer Society.     

Short topotecan-based induction regimen in newly diagnosed high-risk neuroblastoma

Purpose

Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma.

Methods

Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6 mg/m² and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria.

Results

Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable.

Conclusions

These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.     

Comparative efficacy and toxicity of induction chemotherapy with concurrent stereotactic body radiotherapy and stereotactic body radiotherapy with subsequent chemotherapy in patients with clinical stage T1-3N0M0 non-small cell lung carcinoma

Purpose

We compared the clinical efficacy and toxicity of stereotactic body radiotherapy with induction chemotherapy and concurrent radiochemotherapy vs stereotactic body radiotherapy with subsequent chemotherapy in patients with clinical stage T1-3N0M0 non-small cell lung carcinoma.

Methods

We retrospectively analyzed 38 patients with c-stage T1-3N0M0 non-small cell lung carcinoma who received stereotactic body radiotherapy. All patients received six cycles of chemotherapy. Fifteen of the patients were treated with three cycles of induction chemotherapy, one cycle of concurrent radiochemotherapy, and then two cycles of consolidation chemotherapy, while 23 patients received Sequential Radiotherapy/Chemotherapy.

Results

Patients in the induction chemotherapy group experienced a longer duration of esophagitis (median 2 vs 0, range 0–6 vs 0–3.6 weeks, p = 0.04). We divided the patients into two groups based on their median pre-treatment tumor volume (cm³): >32.11 and ≤32.11. The tumor response rate in patients with larger tumor volume was substantially higher in the induction chemotherapy group than in the Sequential Radiotherapy/Chemotherapy group (66.67 vs 40%). Among patients with pre-treatment tumor volume (cm³) >32.11, the median local progression-free survival (LPFS) in the induction chemotherapy group and Sequential Radiotherapy/Chemotherapy group was 18 months (range 7–72 months) and 11 months (range 6–53 months), respectively. There was a statistically significant difference between the two groups (p = 0.006).

Conclusions

Simultaneous SBRT and chemotherapy can result in a longer duration of esophagitis. However, for patients with large tumor volume, ICT combined with concurrent radiochemotherapy may result in better local tumor response as well as longer LPFS and progression-free survival. To better elucidate the best treatment, further clinical trials are needed.

     

Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab

BACKGROUND:

Bevacizumab and sunitinib are standard initial therapy in metastatic renal cell carcinoma (mRCC). Despite common use, the safety and activity of sorafenib in bevacizumab‐ or sunitinib‐refractory mRCC have not been prospectively investigated.

METHODS:

Metastatic RCC patients with Response Evaluation Criteria in Solid Tumors (RECIST)‐defined disease progression (PD) after treatment with either bevacizumab or sunitinib received twice daily 400 mg of sorafenib in a multicenter, prospective phase 2 study. Dose escalation was permitted in the absence of significant toxicity. The primary endpoint was tumor burden reduction rate, defined as the proportion of patients with ≥5% reduction in the sum of RECIST‐defined target lesions without other PD. Secondary endpoints included progression‐free survival (PFS), duration of response, overall survival, and safety. A 2‐stage accrual design was used to test the alternative hypothesis that the tumor burden reduction rate was >20% versus <5%.

RESULTS:

Forty‐eight patients were enrolled. The tumor burden reduction rate was 30% (95% confidence interval [CI], 17%‐45%). One unconfirmed objective partial response was observed. The median PFS was 4.4 months (95% CI, 3.6‐5.9). There was no association of PFS and tumor shrinkage with response to prior therapy. Most treatment‐related adverse events were of mild‐to‐moderate intensity, and included fatigue, hypertension, diarrhea, and palmoplantar erythrodysesthesia (PPE). Patients previously treated with bevacizumab tended to develop more PPE (P = .03) and mucositis (P = .06), whereas sunitinib‐treated patients tended to develop more skin rash (P = .06).

CONCLUSIONS:

Administration of sorafenib is safe and feasible in patients with mRCC refractory to either bevacizumab or sunitinib. Modest clinical activity was observed supporting current practice patterns of sequential vascular endothelial growth factor‐targeted therapy in mRCC. Cancer 2010. © 2010 American Cancer Society.     

Postchemotherapy histological analysis of major intrahepatic vessels for reversal of attachment or invasion by colorectal liver metastases

BACKGROUND:

Although tumor reduction via present‐day prehepatectomy chemotherapy can render initially unresectable disease potentially resectable, little is known about the effects of such chemotherapy on liver metastases with known attachment to or invasion of major intrahepatic vessels. We histologically assessed the relationships of liver tumors to major intrahepatic vessels after chemotherapy.

METHODS:

In 45 patients who underwent chemotherapy and hepatectomy with pretreatment images showing metastases attached to or invading major intrahepatic vessels, 77 metastases showed attachment to or invasion of 96 vessels.

RESULTS:

Using postchemotherapy imaging, 11 of 77 metastases (14.3%) appeared separated from 12 of 96 major hepatic vessels (12.5%). Among 83 vessels later examined pathologically, 29 showed direct invasion (35%) and 10 showed attachment (12%). Tumors involved another 9 vessels (11%) that were separated surgically from the tumor and preserved during hepatectomy. Tumor attachment that exceeded 25% of vessel circumferences via imaging after chemotherapy was a factor associated with pathological vascular invasion or attachment according to multivariate analysis (relative risk, 8.449; 95% confidence interval, 1.961‐36.415; P = .0042).

CONCLUSIONS:

Liver metastasis attachment to or invasion of major intrahepatic vessels is difficult to eradicate even with otherwise effective chemotherapy. Cancer 2012;. © 2011 American Cancer Society.     

Plasma Epstein-Barr virus DNA level strongly predicts survival in metastatic/recurrent nasopharyngeal carcinoma treated with palliative chemotherapy

BACKGROUND:

Plasma Epstein‐Barr virus (EBV) DNA is widely used in screening, monitoring, and prediction of relapse in nonmetastatic nasopharyngeal carcinoma (NPC). However, data regarding utility of plasma EBV DNA in metastatic NPC are rare. The current study was to test the prognostic implication of plasma EBV DNA level in metastatic/recurrent NPC patients treated with palliative chemotherapy.

METHODS:

Plasma EBV DNA level was measured at baseline and thereafter at the start of each treatment cycle in 127 histologically proven metastatic/recurrent NPC patients treated with palliative chemotherapy. Correlations of pre‐treatment and post‐treatment plasma EBV DNA levels to survival and response were analyzed.

RESULTS:

Patients with a low pre‐treatment plasma EBV DNA level ( CONCLUSIONS: Plasma EBV DNA is of predictive value for prognosis in metastatic/recurrent NPC patients undergoing palliative chemotherapy. The pre‐treatment plasma EBV DNA level as well as the early decrease of plasma EBV DNA after chemotherapy enabled easy and early discrimination between patients who will and those who will not benefit from continued treatment. Cancer 2011. © 2011 American Cancer Society.     

Risk of mortality in patients with cancer who experience febrile neutropenia

BACKGROUND:

Febrile neutropenia (FN) is a serious and potentially life‐threatening condition that may develop in patients with cancer who receive myelosuppressive chemotherapy. The risk of mortality from FN is not well characterized in current clinical practice.

METHODS:

Patients with cancer who were receiving chemotherapy in clinical practice were identified from a large US healthcare claims database, and mortality was confirmed using the National Death Index. Patients with FN had their propensity scores matched within tumor types of interest (non‐Hodgkin lymphoma and breast, lung, colorectal, and ovarian cancers) to patients who did not experience FN. Study endpoints of overall mortality (anytime during follow‐up), early mortality (during the first 12 months of the first chemotherapy course), and hospitalization were examined using univariate and multivariate techniques.

RESULTS:

Matched FN and control groups each included 5990 patients, and the average follow‐up for both groups was 17.6 months. Crude incidence rates of early mortality were significantly higher for patients with FN compared with controls for all tumor types. Proportional hazards regression demonstrated a significant increase in the risk of overall and early mortality in patients with FN compared with controls (hazard ratio [HR], 1.15 [95% confidence interval, 1.02‐1.29] and HR, 1.35 [95% confidence interval, 1.09‐1.67], respectively).

CONCLUSIONS:

The adjusted risk of mortality in patients who experienced FN was at least 15% higher than in comparably matched patients without FN, supporting the inference that infectious complications because of neutropenia resulting from myelosuppressive chemotherapy are clinically important. Cancer 2010. © 2010 American Cancer Society.     

Acute pulmonary failure during remission induction chemotherapy in adults with acute myeloid leukemia or high‐risk myelodysplastic syndrome

BACKGROUND:

Acute pulmonary failure during remission induction therapy is a serious complication in patients with acute myeloid leukemia (AML). To the authors' knowledge, the course and prognosis of such patients is not well known.

METHODS:

A total of 1541 patients referred for remission induction chemotherapy of AML or high‐risk myelodysplastic syndrome were retrospectively reviewed.

RESULTS:

A total of 120 (8%) patients developed acute pulmonary failure within 2 weeks of the initiation of chemotherapy; 87 of these patients (73%) died during remission induction, whereas 17 (14%) achieved a complete response. The median survival among the 120 patients with early acute pulmonary failure was 3 weeks. Predictive factors for the development of early acute pulmonary failure by multivariate analysis were: male sex (P = .00038), acute promyelocytic leukemia (P = .00003), poor performance status (P = .001), lung infiltrates at diagnosis (P = .000001), and increased creatinine (P = .000005). Patients who had 0 to 1, 2, 3, or 4 to 5 adverse factors were found to have estimated predictive incidences of acute pulmonary failure of 3%, 13%, 23%, and 34%, respectively.

CONCLUSIONS:

Preventive approaches at the start of induction therapy in patients at high risk of pulmonary failure may improve the outcome of these patients. Cancer 2010. © 2010 American Cancer Society.