Background

The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980's reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution's results of photon radiotherapy for unresectable salivary gland tumors.

Patients and methods

From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. Local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed.

Results

With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient's experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients.

Conclusions

Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.

Background

Although intensity-modulated radiotherapy (IMRT) is a standard of care for many head and neck cancers, its use for carotid-sparing (CS) therapy in early-stage laryngeal carcinoma is controversial.

Methods

330 consecutive patients with early-stage laryngeal carcinoma were treated from 1/1989 to 5/2011, including 282 conventional radiotherapy (CRT) and 48 CS-IMRT patients. The median follow-up was 43 (CS-IMRT) and 66 (CRT) months.

Results

There was no difference in local failure rates comparing patients undergoing CS-IMRT with CRT, with 3-year local control rates of 88% vs. 89%, respectively (p=0.938). Using a 1cm circumferential margin, the average dose to the left and right carotid arteries was 48.3 and 47.9 Gy, respectively. 88% of locoregional recurrences involved the ipsilateral true vocal cord, including all local recurrences in the IMRT group.

Conclusions

These results warrant further prospective evaluation of CS-IMRT for early-stage glottic larynx cancer.

Objectives

To assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC).

Methods

A total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded.

Results

The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; P<0.001), contralateral submandibular gland (45.0 vs. 56.2 Gy; P<0.001), oral cavity (35.9 vs. 45.2 Gy; P<0.001), and contralateral parotid gland (20.0 vs. 24.4 Gy; P<0.001).

Conclusions

Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes.

To develop an automated method for quantifying percent breast density from chest computed tomography (CT) scans. A naïve Bayesian classifier based on gray-level intensities and spatial relationships was developed on CT scans from 10 patients diagnosed with Hodgkin lymphoma (HL) and imaged as part of routine clinical care. The algorithm was validated on CT scans from 75 additional HL patients. The classifier was developed and validated using a reference dataset with consensus manual segmentation of fibroglandular tissue. Accuracy was evaluated at the pixel-level to examine how well the algorithm identified pixels with fibroglandular tissue using true and false positive fractions (TPF and FPF, respectively). Quantitative estimates of the patient-level CT percent density were contrasted to each other using the concordance correlation coefficient, ρc, and to subjective ACR BI-RADS density assessments using Kendalls τb. The pixel-level TPF for identifying pixels with fibroglandular tissue was 82.7% (interquartile range of patient-specific TPFs 65.5%-89.6%). The pixel-level FPF was 9.2% (interquartile range of patient-specific FPFs 2.5%-45.3%). Patient-level agreement of the algorithms automated density estimate with that obtained from the reference dataset was high, ρc = 0.93 (95% CI 0.90-0.96) as was agreement with a radiologists subjective ACR-BI-RADS assessments, τb = 0.77. It is possible to obtain automated measurements of percent density from clinical CT scans.

Purpose

Minor salivary gland cancers are rare and account for roughly 2% to 3% of all head and neck tumors. This is a retrospective review in a modern cohort of patients treated for this rare cancer with surgery and adjuvant radiation therapy.

Materials and methods

Between February 1990 and December 2010, 98 patients with cancer of the minor salivary glands were identified and treated at a single institution. The median radiation dose was 63 Gy. Outcomes assessed included local control (LC), locoregional control (LRC), and overall survival (OS). Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 3.0. Competing-risk analysis using the Gray test was performed, with death as the competing risk. OS was calculated by the Kaplan-Meier method.

Results

With a median follow-up of 7.3 years, the 5- and 10-year LC and LRC rates were 87.9% and 83%, and 80.5% and 73.7%, respectively. Higher T stage and adenocarcinoma histology were the significant negative prognostic factors for both LC and LRC. Freedom from distant metastasis at 5 and 10 years were 83% and 63%, respectively. The median OS was 19.6 years. Overall, no grade 4 or 5 toxicities occurred, and 20% of the cohort experienced an acute grade 3 toxicity, and 6% with a grade 3 late toxicity.

Conclusions

In a modern cohort treated with surgery and radiotherapy, excellent outcomes can be achieved with lower toxicity rates compared with older published series.

Objectives

We previously reported inferior outcomes for locally advanced head and neck cancer treated with cetuximab (C225) versus cisplatin (CDDP). We now examine if this difference persists when accounting for HPV status and update outcomes on the entire cohort.

Materials and methods

From 3/106 to 4/1/08, 174 locally advanced head and neck cancer patients received definitive treatment with RT and CDDP (n=125) or RT and C225 (n=49). Of these, 62 patients had tissue available for HPV analysis.

Results

The median follow-up was 47 months. The 3-year loco-regional failure, disease-free survival, and overall survival for CDDP versus C225 were 5.7% versus 40.2% (P<0.0001), 85.1% versus 35.4% (P<0.0001), and 90.0% versus 56.6% (P<0.0001), respectively. In the subset with tissue, there was no difference in rates of HPV or p16 positivity between the 2 groups. In this subset, the 3-year loco-regional failure, disease-free survival, and overall survival for CDDP versus C225 were 5.3% versus 32.0% (P=0.01), 86.8% versus 43.2% (P=0.002), and 86.7% versus 76.9% (P=0.09), respectively. Multivariate analysis continued to show a benefit for CDDP.

Conclusions

With longer follow-up and the inclusion of HPV and p16 status for about one third of patients where tissue was available, we continued to find superior outcomes with concurrent CDDP versus C225.

Purpose

Synovial sarcoma (SS) is the second most common malignant soft tissue tumor in children. ARST0332 evaluated a risk-based treatment strategy for young patients with soft tissue sarcoma designed to limit therapy for low-risk (LR) disease and to test neoadjuvant chemoradiotherapy for unresected higher-risk disease.

Methods

Newly diagnosed patients with SS age < 30 years were assigned to four treatment arms based on disease features: A (surgery only), B (55.8 Gy radiotherapy [RT]), C (ifosfamide and doxorubicin [ID] chemotherapy plus 55.8 Gy RT), and D (neoadjuvant ID and 45 Gy RT, then surgery and RT boost based on margins followed by adjuvant ID). Patients treated in Arms A and B were considered LR, arms C and D without metastases as intermediate-risk (IR), and those with metastases as high-risk (HR).

Results

Of the 146 patients with SS enrolled, 138 were eligible and evaluable: LR (46), IR (71), and HR (21). Tumors were 80% extremity, 70% > 5 cm, 70% high-grade, 62% invasive, 95% deep, and 15% metastatic. Treatment was on arm A (29.7%), B (3.6%), C (16.7%), and D (50%). There were no toxic deaths and four unexpected grade 4 adverse events. By risk group, at a median follow-up of 6.8 years, estimated 5-year event-free survival was LR 82%, IR 70%, and HR 8%, and overall survival was LR 98%, IR 89%, and HR 13%. After accounting for the features that defined risk category, none of the other patient or disease characteristics (age, sex, tumor site, tumor invasiveness, and depth) improved the risk stratification model.

Conclusion

The risk-based treatment strategy used in ARST0332 produced favorable outcomes in patients with nonmetastatic SS relative to historical controls despite using RT less frequently and at lower doses. The outcome for metastatic SS remains unsatisfactory and new therapies are urgently needed.

Background

The purpose of this study was to report the clinical outcomes and related prognostic factors of patients who underwent radiotherapy (RT) for the treatment of recurrent, never-irradiated oral cavity cancer (recurrent OCC).

Methods

The records of consecutive patients with nonmetastatic recurrent OCC who presented to and were treated with RT at our institution between 1989 and 2011 were reviewed. The Kaplan-Meier method was used to calculate overall survival (OS). The cumulative incidences of disease-specific death, local failure, regional failure, and distant metastasis were calculated with death as a competing risk.

Results

One hundred twenty-three patients were identified. Median follow-up for living patients was 54 months and 16 months for all patients. Ninety-one patients had salvage surgery followed by adjuvant RT. Definitive RT was utilized in the remaining 32 patients. The 5-year OS was 40%. The 5-year cumulative incidence of disease-specific death, local failure, regional failure, and distant metastasis was 55%, 34%, 22%, and 20%, respectively. Recurrent T classification and lack of salvage surgery were independently associated with worse disease-specific death and decreased OS, respectively. Subset analysis of patients who underwent salvage surgery demonstrated that age, recurrent T classification, and perineural invasion (PNI) were independently associated with decreased OS; recurrent T classification and thicker tumors were independently associated with worse disease-specific death; and positive/close margins and primary T classification were independently associated with increased local failure.

Conclusion

In this group of patients with recurrent OCC, clinical outcomes were similar or improved when compared with other recurrent OCC-specific reports. In the salvage surgery subset, tumor thickness and PNI are recurrent pathologic features associated with outcomes that were only previously demonstrated in studies of primary disease. Because of the relatively worse outcomes in patients receiving definitive or adjuvant RT for recurrent OCC, we advocate for the appropriate use of postoperative RT in the initial management of oral cavity cancers.

Background and purpose

Loco-regionally recurrent head and neck cancer (HNC) in the setting of prior radiotherapy carries significant morbidity and mortality. The role of re-irradiation (re-RT) remains unclear due to toxicity. We determined prognostic factors for loco-regional control (LRC) and formulated a nomogram to help clinicians select re-RT candidates.

Material and methods

From July 1996 to April 2011, 257 patients with recurrent HNC underwent fractionated re-RT. Median prior dose was 65 Gy and median time between RT was 32.4 months. One hundred fifteen patients (44%) had salvage surgery and 172 (67%) received concurrent chemotherapy. Median re-RT dose was 59.4 Gy and 201 (78%) patients received IMRT. Multivariate Cox proportional hazards were used to identify independent predictors of LRC and a nomogram for 2-year LRC was constructed.

Results

Median follow-up was 32.6 months. Two-year LRC and overall survival (OS) were 47% and 43%, respectively. Recurrent stage (P=0.005), non-oral cavity subsite (P<0.001), absent organ dysfunction (P<0.001), salvage surgery (P<0.001), and dose >50 Gy (P=0.006) were independently associated with improved LRC. We generated a nomogram with concordance index of 0.68.

Conclusion

Re-RT can be curative, and our nomogram can help determine a priori which patients may benefit.

Purpose

The ARST0332 trial for pediatric and young adults with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) used risk-based treatment including primary resection with lower-than-standard radiation doses to optimize local control (LC) while minimizing long-term toxicity in those requiring radiation therapy (RT). RT for high-grade NRSTS was based on extent of resection (R0: negative margins, R1: microscopic margins, R2/U: gross disease/unresectable); those with >5 cm tumors received chemotherapy (CT; ifosfamide/doxorubicin). This analysis evaluates LC for patients assigned to RT and prognostic factors associated with local recurrence (LR).

Methods and materials

Patients aged <30 years with high-grade NRSTS received RT (55.8 Gy) for R1 ≤5 cm tumor (arm B); RT (55.8 Gy)/CT for R0/R1 >5 cm tumor (arm C); or neoadjuvant RT (45 Gy)/CT plus delayed surgery, CT, and postoperative boost to 10.8 Gy R0 <5 mm margins/R1 or 19.8 Gy for R2/unresected tumors (arm D).

Results

One hundred ninety-three eligible patients had 24 LRs (arm B 1/15 [6.7%], arm C 7/65 [10.8%], arm D 16/113 [14.2%]) at median time to LR of 1.1 years (range, 0.11-5.27). Of 95 eligible for delayed surgery after neoadjuvant therapy, 89 (93.7%) achieved R0/R1 margins. Overall LC after RT were as follows: R0, 106 of 109 (97%); R1, 51 of 60 (85%); and R2/unresectable, 2 of 6 (33%). LR predictors include extent of delayed resection (P <.001), imaging response before delayed surgery (P < .001), histologic subtype (P <.001), and no RT (P = .046). The 5-year event-free survival was significantly lower (P = .0003) for patients unable to undergo R0/R1 resection.

Conclusions

Risk-based treatment for young patients with high-grade NRSTS treated on ARST0332 produced very high LC, particularly after R0 resection (97%), despite lower-than-standard RT doses. Neoadjuvant CT/RT enabled delayed R0/R1 resection in most patients and is preferred over adjuvant therapy due to the lower RT dose delivered.