Patterns of failure in patients with early onset (synchronous) resectable liver metastases from rectal cancer

BACKGROUND:

The optimal combination of available therapies for patients with resectable synchronous liver metastases from rectal cancer (SLMRC) is unknown, and the pattern of recurrence after resection has been poorly investigated. In this study, the authors examined recurrence patterns and survival after resection of SLMRC.

METHODS:

Consecutive patients with SLMRC (disease‐free interval, ≤12 months) who underwent complete resection of the rectal primary and liver metastases between 1990 and 2008 were identified from a prospective database. Demographics, tumor‐related variables, and treatment‐related variables were correlated with recurrence patterns. Competing risk analysis was used to determine the risk of pelvic and extrapelvic recurrence.

RESULTS:

In total, 185 patients underwent complete resection of rectal primary and liver metastases. One hundred eighty patients (97%) received chemotherapy during their treatment course, and 91 patients (49%) received pelvic radiation therapy either before (N = 65; 71.4%), or after (N = 26; 28.6%) rectal resection. The 5‐year disease‐specific survival rate was 51% for the entire cohort with a median follow‐up of 44 months for survivors. One hundred thirty patients (70%) developed a recurrence: Eighteen patients (10%) had recurrences in the pelvis in combination with other sites, and 7 of these (4%) had an isolated pelvic recurrence. Recurrence pattern did not correlate with survival. Competing risk analysis demonstrated that the likelihood of a pelvic recurrence was significantly lower than that of an extrapelvic recurrence (P < .001).

CONCLUSIONS:

Of the patients with SLMRC who developed recurrent disease, systemic sites were overwhelmingly more common than pelvic recurrences. The current results indicated that the selective exclusion of radiotherapy may be considered in patients who are diagnosed with simultaneous disease. Cancer 2012. © 2012 American Cancer Society.     

Prognostic factors and long‐term outcomes of childhood nasopharyngeal carcinoma

BACKGROUND:

The authors studied the survival and long‐term morbidities of children with nasopharyngeal carcinoma (NPC).

METHODS:

This was a retrospective review of children with NPC who were treated at St. Jude Children's Research Hospital between 1961 and 2004. Prognostic factors and long term effects of therapy were analyzed.

RESULTS:

Fifty‐nine patients (median age, 14.1 years) were identified. Most were male (66.1%) and black (54.2%) and had lymphoepithelioma (93.2%). Thirty‐five patients had stage IV disease (59.3%), 20 patients had stage III disease (33.9%), and 4 patients had stage II disease (6.8%). All patients received radiotherapy (RT) to the primary tumor, and most received cervical RT (98.3%) and chemotherapy (88.1%). The 15‐year survival and event‐free survival (EFS) rates were 67.2% ± 7.5% and 63.5% ± 7.8%, respectively. Five patients (8.5%) developed subsequent malignancies 8.6 to 27 years after NPC diagnosis. EFS was improved in patients who were diagnosed after 1980 (74.8% ± 10% vs 45.5% ± 10.1%; P = .031), in patients who had stage III disease compared with patients who had stage IV disease (79.3% ± 9.6% vs 56.2% ± 11.8%; P = .049), in patients who received cisplatin (81% ± 10.7% vs 45.8% ± 9.7%; P = .013), and in patients who received ≥50 grays of RT (71.4% ± 9.3% vs 43.8% ± 11.6%; P = .048). White patients had higher distant failure rates than black patients (41.7% ± 10.4% vs 15.6 ± 6.5%; P = .045). The 15‐year cumulative incidence (CI) of any morbidity was 83.7% ± 5.4%, the CI of sensorineural hearing loss was 52.9% ± 6.7%, the CI of primary hypothyroidism was 42.7% ± 6.6%, and the CI of growth hormone deficiency (GHD) was 14.1% ± 4.7%. Dose‐response relations were observed between the RT dose and primary hypothyroidism and GHD.

CONCLUSIONS:

The outcome of children with NPC improved over the past 4 decades with the use of cisplatin‐based chemotherapy and higher RT doses. However, many survivors had long‐term treatment‐related morbidities. Cancer 2011. © 2010 American Cancer Society.     

Change in treatment strategy for intracranial germinoma: long-term follow-up experience at a single institute

BACKGROUND:

Previous intracranial germinoma (IG) studies have investigated the effect of different radiotherapy (RT) volumes and the necessity for adjunctive chemotherapy, but there is currently no consensus on the best treatment for this tumor.

METHODS:

From January 1989 to December 2009, 80 IG patients (≤20 years old) were treated with various RT regimens. Of them, 14 patients had craniospinal irradiation (CSI) + primary boost (PB); 8 patients had whole‐brain irradiation (WBI) + PB; 31 patients had whole ventricular irradiation (WVI) + PB; and 27 patients had focal RT only. Twenty‐nine patients (36.2%) also received systemic chemotherapy (CHT). Survival was estimated by the Kaplan‐Meier method and variables affecting survival were analyzed by the Cox proportional hazard model.

RESULTS:

Eleven patients (13.8%) developed local recurrence or dissemination after treatment, and 10 of these patients were in the focal RT group. The 5‐year relapse‐free survival (RFS) for the CSI, WBI, WVI, and focal RT patients were 100%, 85.7%, 100%, and 84.6%, respectively (P = .001). The 5‐year overall survival (OS) for CSI, WBI, WVI, and focal RT patients was 100%, 83.3%, 100%, and 87.9%, respectively (P = .125). Focal irradiation (P = .02) and initial use of CHT (P = .021) were negatively associated with RFS.

CONCLUSIONS:

Focal RT plus CHT were associated with inferior control of IG and a higher incidence of CHT‐related toxicities. Adjustment of the radiation volume to the whole ventricular system without CHT is sufficient for treatment of nondisseminated IGs, even with lower primary RT doses (<36 Gy). Cancer 2011. © 2011 American Cancer Society.     

High‐dose chemotherapy and autologous hematopoietic progenitor cell rescue in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors

BACKGROUND:

The role of myeloablative chemotherapy in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors (MB/ST‐PNET) is controversial, in particular in patients who develop recurrent disease after craniospinal radiotherapy.

METHODS:

In this retrospective analysis, the authors investigated the outcome of children with recurrent MB/ST‐PNET who were referred for myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue at Childrens Hospital Los Angeles.

RESULTS:

Thirty‐three children were referred for myeloablative chemotherapy: Fourteen of those children were never transplanted because of pre‐transplant adverse events, and 19, including 6 without and 13 with previous irradiation, underwent transplant. Conditioning regimens included a backbone of thiotepa, which was given either in a single cycle or in multiple sequential cycles. The 3‐year post‐transplant event‐free survival rate in unirradiated versus previously irradiated children was 83% ± 15% versus 20% ± 12%, respectively (P = .04). One child who had never been exposed to radiotherapy died of toxicity; the other children received post‐transplant radiotherapy and remained disease free. Nine previously irradiated children experienced 4 toxic deaths and 6 tumor recurrences (1 patient had both): An interval of <1 year between initial radiotherapy and myeloablative chemotherapy predicted a greater risk of toxic death (P = .02), whereas a history of meningeal metastases at diagnosis and a poor response to the initial rescue therapy predicted a greater risk of post‐transplant recurrence (P = .03 and P = .08, respectively).

CONCLUSIONS:

Myeloablative doses of thiotepa‐based chemotherapy and radiotherapy were able to cure most children who had radiotherapy‐naive, chemoresponsive recurrences. Children who developed recurrences after craniospinal radiotherapy had poorer outcomes; however, cure was possible in those who had good prognostic features at presentation, chemoresponsive recurrences, and a long interval between initial radiotherapy and myeloablative chemotherapy. Cancer 2009. © 2009 American Cancer Society.     

The diagnostic and prognostic utility of positron emission tomography/computed tomography‐based follow‐up after radiotherapy for head and neck cancer

BACKGROUND:

The detection of subclinical head and neck cancer recurrence or a second primary tumor may improve survival. In the current study, the authors investigated the clinical value of a follow‐up program incorporating serial ¹⁸F?fluorodeoxyglucose?positron emission tomography integrated with computed tomography (PET/CT) in the detection of recurrent disease in patients with head and neck cancer.

METHODS:

A total of 240 PET/CT scans were reviewed in 80 patients with head and neck cancer who were treated with radiotherapy (RT) from July, 2005 through August, 2007. All patients were followed with clinical examination, PET/CT, and correlative imaging for a minimum of 11 months (median follow?up, 21 months).

RESULTS:

The sensitivity, specificity, and positive and negative predictive values of PET/CT‐based follow‐up for detecting locoregional recurrence were 92%, 82%, 42%, and 98%, respectively. Corresponding values for distant metastases or second primary tumors were 93%, 96%, 81%, and 98%, respectively. Eight patients (10%) developed disease recurrences or second primary tumors that were amenable to salvage surgery with negative surgical margins. The 2‐year progression‐free survival and 2‐year overall survival rates were significantly different between patients who had a negative and those with a positive PET/CT result within 6 months of the completion of RT (93% vs 30% [P<.001] and 100% vs 32% [P<.001], respectively).

CONCLUSIONS:

Although post‐therapy follow‐up using PET/CT is reportedly associated with a high false‐positive rate in the irradiated head and neck, PET/CT appears to be a highly sensitive technique for the detection of recurrent disease. Furthermore, negative PET/CT results within 6 months of the completion of RT offer significant prognostic value. Cancer 2009. © 2009 American Cancer Society.     

Outcomes of malignant tumors of the lacrimal apparatus: the University of Texas MD Anderson Cancer Center experience

BACKGROUND:

Malignant epithelial neoplasms of the lacrimal apparatus are rare and are typically treated with surgery and occasionally adjuvant radiation therapy (RT). The purpose of this study was to assess treatment outcomes by type of surgery (orbital exenteration vs eye‐sparing surgery) and clarify the role of adjuvant RT for this rare disease.

METHODS:

Forty‐six patients with malignant epithelial neoplasms of the lacrimal apparatus were treated at a single institution from 1945 through 2008. Twenty‐seven patients (59%) were treated with orbital exenteration and 19 (41%) with eye‐sparing surgery; 64% of the orbital exenteration group and 83% of the eye‐sparing surgery group also received adjuvant RT (median dose, 60 grays). Median follow‐up time for all patients was 38 months (range, 3‐460 months).

RESULTS:

For the orbital exenteration and eye‐sparing surgery groups, the 5‐year overall survival (OS) rates were 59% and 62%, and the 5‐year disease‐free survival (DFS) rates were 49% and 39%, respectively (P = .56, P = .35). Tumor status (T1‐2 vs T3‐4) was associated with OS (P = .02), and tumor size (<3.5 vs >3.5 cm) with DFS (P = .015). Median time to locoregional recurrence was 85 months for orbital exenteration, and 123 months for eye‐sparing surgery. All patients who did not receive RT experienced local recurrence, and RT extended time to locoregional recurrence (median 460 vs 30 months, P = .009). Seven grade ≥3 complications were experienced after adjuvant RT.

CONCLUSIONS:

For appropriately selected patients, an eye‐sparing surgery for lacrimal apparatus tumors can achieve similar survival outcomes to those in patients treated with an orbital exenteration. Adjuvant RT should be considered for all patients presenting with these rare tumors. Cancer 2011. © 2011 American Cancer Society.     

Treatment of epidural spinal cord involvement from germ cell tumors with chemotherapy

BACKGROUND:

Germ cell tumors (GCTs) are chemosensitive, and epidural spinal cord compression (ESCC) from GCT may be amenable to treatment with chemotherapy (CT) only. This retrospective study compares the clinical outcome of GCT patients with ESCC treated with CT or radiotherapy (RT) + CT.

METHODS:

All patients with a histologic diagnosis of GCT from 1984 to 2009 were included in this study. Patients with ESCC were identified. Age, clinical features, histology, treatment, and outcome were analyzed.

RESULTS:

The authors identified 1734 patients with GCT, of whom 29 (1.7%) had ESCC. The median age of these 29 patients was 32 years. The ESCC was treated with CT only in 16, RT + CT in 11, and 2 patients received palliative care only. The ESCC was more extensive in the RT + CT than the CT group. Patients who received RT + CT had a higher proportion of failed prior CT regimens, a higher percentage of nonseminomatous GCT, T‐spine involvement, multilevel epidural disease, and bony vertebral metastases. Median overall survival after diagnosis of ESCC was not reached for those treated with CT alone versus 15 months for those receiving RT + CT (P = .02). There was also a significant difference in survival in patients receiving first‐line therapy (n = 15), where median overall survival was not reached in the CT group (n = 11), compared with 22 months in the RT group (n = 4) (P = .04).

CONCLUSIONS:

GCTs rarely involve the epidural compartment. Patients with ESCC who are likely to have chemosensitive disease can receive CT alone as definitive treatment. Cancer 2011. © 2010 American Cancer Society.     

Long-term follow-up of patients treated with neoadjuvant chemotherapy and radiotherapy for large, extremity soft tissue sarcomas

BACKGROUND:

Patients with large, high‐grade, extremity soft tissue sarcomas (STS) are at significant risk for distant recurrence and death. A regimen of preoperative chemotherapy consisting of mesna, Adriamycin (doxorubicin), ifosfamide, and dacarbazine (MAID), interdigitated with radiotherapy (RT) and followed by resection and postoperative chemotherapy with or without RT, has demonstrated high rates of local and distant control. We report the long‐term follow‐up data on 48 patients treated with this regimen compared to an historical matched‐control patient population.

METHODS:

Adult patients with high‐grade extremity STS ≥ 8 cm were treated with 3 cycles of preoperative chemotherapy combined with 44 Gy of RT followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy of RT was delivered postoperatively.

RESULTS:

Patients received the MAID/RT regimen from 1989 through 1999. After a median follow‐up of 9.3 years in surviving patients in the MAID group and 13.2 years in surviving patients in the control group, the 7‐year disease‐specific and overall survival rates were 81% and 50% (P = .004) and 79% and 45% (P = .003) for the MAID and control patients, respectively. Five of 11 patients in the MAID group and 7 of 25 control patients died of sarcoma ≥5 years after treatment. One patient in the MAID group developed a fatal myelodysplasia at 53 months.

CONCLUSIONS:

For patients with high‐risk, extremity STS, the significant survival benefits conferred by an intense regimen of neoadjuvant chemoradiotherapy and surgery are sustained even with long‐term follow‐up. Cancer 2012. © 2011 American Cancer Society.     

Outcomes after adjuvant chemotherapy in the treatment of high-risk urothelial carcinoma of the upper urinary tract (UUT-UC): results from a large multicenter collaborative study

BACKGROUND:

Urothelial carcinoma of the upper urinary tract (UUT‐UC) was a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. High‐risk patients had poor outcomes. Because of the rarity of these tumors, randomized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable. Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high‐risk, postsurgical UUT‐UC patients.

METHODS:

Using a multi‐institutional, international retrospective database, identified were 627 patients with high risk UUT‐UCs (pT3N0, pT4N0 and/or N+ and/or M+) who underwent surgical removal. Only patients who received adjuvant chemotherapy were included.

RESULTS:

Overall, 140 patients (22.6%) with a median age of 67 years were included. The median follow‐up was 22.5 months. The 5‐year, overall survival for the entire cohort was 43%, the 5‐year recurrence‐free survival was 54%, and metastasis‐free survival was 53% at 5 years. Positive surgical margins were an independent prognostic factor for recurrence (P = .06), cancer‐specific mortality (P = .05), and overall mortality (P = .02) of any cause. Adjuvant chemotherapy was not linked with overall or cancer‐specific survival in patients with high risk disease (adjuvant chemotherapy [n = 140] vs no treatment [n = 487]) (P >.5).

CONCLUSIONS:

Adjuvant postoperative chemotherapy did not offer any significant benefit to overall survival in our population. Additional data were necessary, and studies enrolling patients at high risk in clinical trials investigating neoadjuvant chemotherapy in conjunction with chemotherapy should have been highly encouraged. Cancer 2011;. © 2011 American Cancer Society.     

Integration of radiotherapy and chemotherapy for abdominal lymph node recurrence in gastric cancer

Purpose

Abdominal lymph node (ALN) recurrence in gastric cancer (GC) is rare and usually unresectable. We investigated the effects of integration of radiotherapy (RT) and chemotherapy against ALN recurrence in GC.

Methods

We retrospectively categorized GC patients with ALN recurrence treated between 2005 and 2013 into two groups: those treated with integration of RT and chemotherapy (RCT) and those who received systemic chemotherapy only (CT). The median follow-up period after ALN recurrence for all patients was 20 months.

Results

Of 53 patients, 31 and 22 were in the RCT and CT groups, respectively. Isolated distant failure (DF; 35.5%) without local progression (LP) was the dominant pattern of failure (POF) in the RCT group (median DF-free period, 26 months). LP followed by DF (31.8%) was the dominant POF in the CT group; LP (median LP-free period, 8 months) occurred 10 months earlier than DF (median DF-free period, 18 months). RCT patients had significantly longer median progression-free survival (PFS) compared to CT patients (25 vs. 8 months; P = 0.021). On multivariate analysis, treatment (CT vs. RCT) was an independent prognostic factor for PFS (hazard ratio 2.085; 95% confidence interval 1.073–4.050; P = 0.013).

Conclusions

Integration of RT and chemotherapy achieved long-term local control and prolonged PFS in GC patients with ALN recurrence. Local RT is feasible for treating isolated ALN recurrences.

     

Metastatic cutaneous squamous cell carcinoma to parotid nodes: the role of bolus with adjuvant radiotherapy

Introduction: Information regarding the addition of tissue equivalent bolus to adjuvant radiotherapy (RT) for intra‐parotid metastatic head and neck cutaneous squamous cell carcinoma is lacking. This study aimed to evaluate the effect of bolus versus no bolus on the patterns of regional and distant recurrence, regional control (RC), cancer‐specific survival (CSS), overall survival, RT toxicity and RT interruption. Methods: A retrospective study was performed on consecutive patients diagnosed between 1994 and 2008 with metastatic head and neck cutaneous squamous cell carcinoma who were treated with parotidectomy ± selective neck dissection and adjuvant RT ± parotid bolus. Results: Seventy‐five patients were identified: 64 males and 11 females, with median age of 79 years (range 40–96) of which 39 had bolus during RT. Median follow up was 48 months (range 4–177). There were 23 regional recurrences – 14 dermal, six dermal + nodal and three isolated nodal – and only two systemic recurrences. Nine patients had RT interruption >6 days due to acute skin toxicity. Bolus was associated with increased grade ≥3 radiation dermatitis (P = 0.02). RT interruption >6 days was significantly associated with inferior RC and hazard ratio, 2.83 (95% confidence interval: 1.04–7.71, P = 0.042). Lympho‐vascular space invasion, positive margins and nodes >2 cm were adversely significant on CSS multivariate analysis. RC, CSS and overall survival at 5 years were 67, 66 and 52%, respectively. Conclusions: Dermal involvement dominated the pattern of regional recurrence. Bolus was associated with significantly worse skin reaction. Bolus use was not associated with a significant overall benefit on RC. This analysis does not support the use of bolus as applied in this cohort.     

Endoscopic ultrasound and computed tomography in restaging and predicting prognosis after neoadjuvant chemotherapy in patients with locally advanced gastric cancer

BACKGROUND.

The objective of the current study was to assess the staging accuracy and prognostic role of preoperative endoscopic ultrasound (EUS) and computed tomography (CT) in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy.

METHODS.

Presurgical LAGC patients underwent EUS and CT before and after 3 cycles of neoadjuvant chemotherapy. Chemotherapy was comprised of docetaxel (at a dose of 36 mg/m²) and cisplatin (at a dose of 40 mg/m²) on Days 1 and 8 of a 3‐week cycle.

RESULTS.

Forty patients were enrolled in the study. After chemotherapy, the accuracy of EUS and CT was found to be 47% and 57%, respectively for T classification (P = .22) and 39% and 37%, respectively for N classification (P > .99). The 3‐year overall survival (OS) rate for patients downstaged with EUS for T and/or N classification was greater than that for nondownstaged patients (69% vs 41%; P = .05). The 2‐year recurrence‐free survival (RFS) rate was also better for the EUS‐downstaged patients than for the nondownstaged patients (77% vs 47%; P = .04). On multivariate analysis, EUS downstaging was found to be correlated with OS (hazards ratio [HR] of 0.12; P = .04), and was correlated with RFS with borderline statistical significance (HR of 0.27; P = .07). The differences in OS and RFS between the patients downstaged with CT and those not downstaged were not found to be statistically significant.

CONCLUSIONS.

Restaging by EUS and CT after neoadjuvant chemotherapy in patients with LAGC was found to be inaccurate. However, T and/or N downstaging by EUS was found to be correlated with better OS and RFS. Thus, downstaging by EUS may be a useful clinical parameter with which to predict a better outcome for LAGC patients. Cancer 2008. © 2008 American Cancer Society.     

Long‐term outcomes for patients with limited stage follicular lymphoma

BACKGROUND:

Given the indolent behavior of follicular lymphoma (FL), it is controversial whether limited stage FL can be cured using radiotherapy (RT). Furthermore, the optimal RT field size is unclear. The authors of this report investigated the long‐term outcomes of patients with limited stage FL who received RT alone and studied the impact of reducing the RT field size from involved regional RT (IRRT) to involved node RT with margins up to 5 cm (INRT≤5 cm).

METHODS:

Eligible patients had limited stage, grade 1 through 3A FL diagnosed between 1986 and 2006 and treated were with curative‐intent RT alone. IRRT encompassed the involved lymph node group plus ≥1 adjacent, uninvolved lymph node group(s). INRT≤5 cm covered the involved lymph node(s) with margins ≤5 cm.

RESULTS:

In total, 237 patients were identified (median follow‐up, 7.3 years) and included 48% men, 54% aged >60 years, stage IA disease in 76% of patients, elevated lactate dehydrogenase (LDH) in 7% of patients, grade 3A tumors in 12% of patients, and lymph node size ≥5 cm in 19% of patients. The 2 RT groups were IRRT (142 patients; 60%) and INRT≤5 cm (95 patients; 40%). At 10 years, the progression‐free survival (PFS) rate was 49%, and the overall survival (OS) rate was 66%. Only 2 patients developed recurrent disease beyond 10 years. The most common pattern of first failure was a distant recurrence only, which developed in 38% of patients who received IRRT and in 32% of patients who received INRT≤5 cm. After INRT≤5 cm, 1% of patients had a regional‐only recurrence. Significant risk factors for PFS were lymph nodes ≥5 cm (P = .008) and male gender (P = .042). Risk factors for OS were age >60 years (P < .001), elevated LDH (P = .007), lymph nodes ≥5 cm (P = .016), and grade 3A tumors (P = .036). RT field size did not have an impact on PFS or OS.

CONCLUSIONS:

Disease recurrence after 10 years was uncommon in patients who had limited stage FL, suggesting that a cure is possible. Reducing RT fields to INRT≤5 cm did not compromise long‐term outcomes. Cancer 2010. © 2010 American Cancer Society.     

Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence

BACKGROUND:

In head and neck cancer (HNC), 3‐month post‐treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post‐treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months.

METHODS:

A 10‐year retrospective analysis of HNC patients was carried out with long‐term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3‐month scans, 175 had 3‐ and 12‐month scans, and 77 had 3‐, 12‐, and 24‐month scans.

RESULTS:

PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT‐detected and clinically detected recurrences, with similar 3‐year disease‐free survival (41% vs 46%, P = .91) and 3‐year overall survival (60% vs 54%, P = .70) rates. Compared with 3‐month PET/CT, 12‐month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive.

CONCLUSIONS:

HNC patients with negative 3‐month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT‐detected and clinically detected recurrences, although larger prospective studies are needed for further investigation. Cancer 2013. © 2012 American Cancer Society.     

Genetic alterations between primary head and neck squamous cell carcinoma and recurrence after radiotherapy

BACKGROUND:

In the attempt to characterize the genetic bases of recurrent head and neck squamous cell carcinoma (HNSCC) after radiotherapy (RT), the authors compared the molecular profiles of primary tumors and recurrences.

METHODS:

TP53 gene status and instability at 10 microsatellite markers were determined in pre‐RT lesions and corresponding local recurrences in a series of 16 HNSCCs.

RESULTS:

Eight (50%) HNSCCs showed both TP53 and microsatellite instability (MSI) status concordance in pre‐ and postirradiation biopsies; 3 (18.7%) showed discordance of both TP53 and MSI status; and finally 5 (31.2%) had discordance at only 1 genetic test. Accordingly, the authors interpreted as true recurrence the 8 concordant cases, and as true second primary malignancies the 3 discordant ones. In the remaining 5 cases with partial DNA correspondence, the exact nature of the new lesion only partially related to the original cancer is a matter of discussion. Patients showing the same mutations among pre‐ and post‐RT HNSCCs had a longer disease‐free interval (DFI) and better survival than those showing discordant genetic features (log‐rank test, P = .0045).

CONCLUSIONS:

Post‐RT recurrent HNSCCs are genetically heterogeneous. The genetic characterization of the recurrence, especially in those cases with a particularly short DFI showing partially discordant mutations, might have a useful clinical relevance in the restaging process. Cancer 2010. © 2010 American Cancer Society.     

The role of salvage surgery in patients with recurrent squamous cell carcinoma of the oropharynx

BACKGROUND:

The objective of this study was to comprehensively review overall survival, functional outcomes, and prognostic factors in patients who underwent salvage surgery for locally recurrent squamous cell carcinoma of the oropharynx (SCCOP) after initial radiotherapy.

METHODS:

The authors retrospectively reviewed 1681 consecutive patients who completed definitive therapy for primary SCCOP and identified 168 patients with locally recurrent SCCOP who underwent salvage surgery (41 patients), reirradiation or brachytherapy (18 patients), palliative chemotherapy (70 patients), or supportive care (39 patients).

RESULTS:

Twenty‐six of 39 patients (67%) developed a second recurrence after salvage surgery. The 3‐year overall survival rate for patients who underwent salvage surgery or received reirradiation, palliative chemotherapy, or supportive care were 48.7%, 31.6%, 3.7%, and 5.1%, respectively. For patients who underwent salvage surgery, older age (P = .03), the absence of a disease‐free interval (P < .01), and advanced recurrent tumor stage (P = .07) were associated with lower overall survival. Patients with recurrent neck disease (P = .01) and positive surgical margins (P = .04) had higher rates of recurrence after salvage surgery. Postoperative complications occurred in 19 patients (46%), and there were no perioperative deaths. Functionally, 71% of patients demonstrated ≥80% speech intelligibility, 68% were able to tolerate some oral intake, and 87% who required a tracheotomy subsequently were decannulated.

CONCLUSIONS:

Age, disease‐free interval, recurrent tumor stage, recurrent neck disease, and surgical margin status influenced overall survival or recurrence rate after salvage surgery for recurrent SCCOP. Although most patients had good functional outcomes, only a select group of patients with recurrent SCCOP achieved long‐term survival after salvage surgery. Cancer 2009. © 2009 American Cancer Society.     

Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma

BACKGROUND:

Although adjuvant chemoradiation is used commonly in the United States for the treatment of resected pancreatic cancer, there is no consensus on the benefit of this therapy, because the results from randomized trials are conflicting. The authors of this report reviewed their experience in a consecutive, unselected series of patients who received adjuvant 5‐fluorouracil (5‐FU) and radiation therapy (RT) for resected pancreatic adenocarcinoma.

METHODS:

Eighty‐six patients with resected pancreatic adenocarcinoma who received adjuvant therapy from 1998 to 2005 were identified, and their medical records were reviewed. Ninety‐three percent of patients were treated with external beam RT to ≥50.4 grays, and 91% of patients received concurrent 5‐FU by continuous infusion. Forty‐five percent of patients went on to receive adjuvant gemcitabine.

RESULTS:

The median follow‐up was 31 months (range, 21‐62 months) among the 20 patients who remained alive. Less than half of patients had positive (33%) or close (<1 mm; 15%) resection margins, 81% of tumors were classified as T3, and 66% of patients had involved lymph nodes. The median overall survival (OS) for all patients was 22 months. Negative lymph node status (P = .016) was a significant prognostic factor for improved OS, whereas treatment with gemcitabine trended toward improved OS (P = .080). The median disease‐free survival (DFS) for all patients was 10 months: Treatment with gemcitabine (P = .044) and the receipt of any chemotherapy (P = .047) were significant predictors of DFS. Seventy‐five patients (87%) had disease recurrence, and the majority recurred with peritoneal metastases (55%) or liver metastases (53%). Patients who had negative lymph nodes trended toward a lower rate of distant failure (P = .060).

CONCLUSIONS:

The median survival of the current cohort was greater than that of the chemoradiation arms of European Organization for Research and Treatment of Cancer trials and European Study Group for Pancreatic Cancer 1 trials and was comparable to the survival observed on the Gastrointestinal Tumor Study Group chemoradiation arm. Lymph node status and treatment with adjuvant chemotherapy were significant predictors of OS and DFS, respectively. Future survival improvements should be directed at reducing peritoneal and liver metastases. Further randomized trials will be required to define the role of adjuvant therapy for pancreatic adenocarcinoma. Cancer 2009. © 2009 American Cancer Society.     

Survival in patients with metastatic recurrent breast cancer after adjuvant chemotherapy

BACKGROUND:

Population‐based studies have shown improved survival for patients diagnosed with metastatic breast cancer over time, presumably because of the availability of new and more effective therapies. The objective of the current study was to determine whether survival improved for patients who developed distant recurrence of breast cancer after receiving adjuvant therapy.

METHODS:

Adjuvant chemotherapy trials coordinated by the Eastern Cooperative Oncology Group that accrued patients between 1978 and 2002 were reviewed. Survival after distant disease recurrence was estimated for progressive time periods, and adjusted for baseline covariates in a Cox proportional hazards model.

RESULTS:

Of the 13,785 patients who received adjuvant chemotherapy in 11 trials, 3447 (25%) developed distant disease recurrence; the median survival after recurrence was 20 months (95% confidence interval, 19 months‐21 months). Factors associated with inferior survival included a shorter distant recurrence‐free interval (DRFI), estrogen receptor‐negative and progesterone receptor‐negative disease, the number of positive axillary lymph nodes present at the time of diagnosis, and black race (P < .0001 for all). When the time period of recurrence was added to the model, it was not found to be significantly associated with survival for the general population with disease recurrence. Survival improved over time only in those patients with hormone receptor‐negative disease with a DRFI ≤ 3 years, both among the 5 most recent and the entire trial data sets (P = .01 and P = .05, respectively).

CONCLUSIONS:

In contrast to reports from population‐based studies, no general improvement in survival was observed over the last 30 years for patients who developed distant disease recurrence after adjuvant chemotherapy after adjusting for DRFI. Improved survival for patients with hormone receptor‐negative disease with a short DRFI suggests a benefit from trastuzumab. Cancer 2013. © 2012 American Cancer Society.     

Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer

BACKGROUND:

The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node‐negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status.

METHODS:

The authors reviewed 704 women with T1aT1bN0M0 BC who received treatment at the Radiation‐Oncology Center of Florence University between November 2002 and December 2008. Patients with ductal carcinoma in situ or recurrent BC at presentation and patients who received adjuvant chemotherapy were excluded from the analysis.

RESULTS:

In total, 75 patients had HER2‐positive BC (10.7%). At a mean follow‐up of 4.9 years (standard deviation, 2.6 years; range, 0.5‐10.8 years), 19 events were identified, including 10 distant recurrences. Patients with HER2‐positive BC had worse distant recurrence‐free survival (DRFS) than patients with HER2‐negative BC (hazard ratio, 3.66; 95% confidence interval, 0.94‐14.69; P = .045). Negative hormone receptor (HR) status was associated significantly with worse DRFS (hazard ratio, 0.26; 95% confidence interval, 0.07‐0.93; P = .026). In multivariate analysis, younger age was the only significant risk factor for an event of recurrence (hazard ratio, 0.61;95% confidence interval, 0.20‐1.82; P = .029).

CONCLUSIONS:

The current results indicated that patients with T1a/T1b, lymph node‐negative BC have a low risk of distant and local recurrence, but younger age is a significant risk factor for events occurrence. Young women with HER2‐positive and HR‐negative status have a significant risk of distant recurrence and should be considered for future clinical trials with anti‐HER2 adjuvant therapy. Cancer 2011. © 2011 American Cancer Society.     

Local, regional, and systemic recurrence rates in patients undergoing skin-sparing mastectomy compared with conventional mastectomy

BACKGROUND:

Although the use of SSM is becoming more common, there are few data on long‐term, local‐regional, and distant recurrence rates after treatment. The purpose of this study was to examine the rates of local, regional, and systemic recurrence, and survival in breast cancer patients who underwent skin‐sparing mastectomy (SSM) or conventional mastectomy (CM) at our institution.

METHODS:

Patients with stage 0 to III unilateral breast cancer who underwent total mastectomy at our center from 2000 to 2005 were included in this study. Kaplan‐Meier curves were calculated, and the log‐rank test was used to evaluate the differences between overall and disease‐free survival rates in the 2 groups.

RESULTS:

Of 1810 patients, 799 (44.1%) underwent SSM and 1011 (55.9%) underwent CM. Patients who underwent CM were older (58.3 vs 49.3 years, P<.0001) and were more likely to have stage IIB or III disease (53.0% vs 31.8%, P<.0001). Significantly more patients in the CM group received neoadjuvant chemotherapy and adjuvant radiation therapy (P<.0001). At a median follow‐up of 53 months, 119 patients (6.6%) had local, regional, or systemic recurrences. The local, regional, and systemic recurrence rates did not differ significantly between the SSM and CM groups. After adjusting for clinical TNM stage and age, disease‐free survival rates between the SSM and CM groups did not differ significantly.

CONCLUSIONS:

SSM is an acceptable treatment option for patients who are candidates for immediate breast reconstruction. Local‐regional recurrence rates are similar to those of patients undergoing CM. Cancer 2011. © 2010 American Cancer Society.