Daniel E. Fass

The indications for elective treatment of the neck in cancer of the major salivary glands

To define the indications for elective neck treatment, the cases of 474 previously untreated patients were reviewed who had locally confined major salivary gland cancers treated between 1939 and 1982, Clinically positive nodes were present in 14% (67 of 474). Overall, clinically occult, pathologically positive nodes occurred in 12% (47 of 407). By univariate analysis, several factors appeared to predict the risk of occult metastases; however, multivariate analysis revealed that only size and grade were significant risk factors. Tumors 4 cm or more in size had a 20% (32 of 164) risk of occult metastases compared with a 4% (nine of 220) risk for smaller tumors [P < 0.00001). High‐grade tumors (regardless of histologic type) had a 49% (29 of 59) risk of occult metastases compared with a 7% (15 of 221) risk for intermediate‐grade or low‐grade tumors [P < 0.00001). In view of the low frequency of occult metastases in the entire group, routine elective treatment of the neck is not recommended. High‐grade tumors and larger tumors have a high rate of occult neck metastases, and treatment should be considered in this group.

Improved dose distributions for 3d conformal boost treatments in carcinoma of the nasopharynx

This study was designed to demonstrate the feasibility of 3-dimensional (3D) treatment planning in patients with carcinoma of the nasopharynx, and to explore its potential therapeutic advantage over the traditional 2-dimensional (2D) approach in this disease. Qualitative and quantitative comparisons between the two techniques were made for the boost portion of the treatment (19.8 Gy of a total 70.2 Gy treatment schedule) in 10 previously untreated patients and for the entire treatment in 5 patients with locally recurrent disease. The 2D and 3D plans were compared in each patient using dose-volume histograms (DVHs), tumor control probabilities (TCPs), normal tissue complication probabilities (NTCPs), and a new biologic figure of merit that describes the probability of uncomplicated control. Although there was no attempt to optimize the 3D treatment approach by using this method throughout the total treatment course (rather than for the boost only), it was still found that for each of the endpoints examined the 3D approach resulted in improved plans. An average of 22% of the target volume was underdosed at the 95% isodose level with the 2D plans compared to 7% with the 3D plans. The improved treatment planning by 3D increased the mean dose to the tumor volume by an average of 13% over 2D planning. The dose to normal structures such as the mandible and parotid glands was reduced with the 3D plans while the brain stem and spinal cord remained within tolerance limits. The probability of uncomplicated tumor control was increased by an average of 15% with 3D treatment planning compared to the 2D approach. Our findings demonstrate the potential of 3D planning for improving the treatment of carcinoma of the nasopharynx, but prospective studies are required to define the true clinical advantages of this methodology.

Postoperative radiation therapy for squamous cell carcinomas of the oral cavity and oropharynx: Impact of therapy on patients with positive surgical margins

PURPOSE The presence of a positive or close margin after resection of a squamous cancer of the head and neck is associated with a significant risk of local recurrence. To determine the efficacy of postoperative radiation therapy for patients with advanced oral cavity and oropharyngeal cancers with inadequate margins of resection, the present retrospective analysis was undertaken. METHODS AND MATERIALS One hundred and two patients were treated with surgery and postoperative radiation therapy for advanced squamous cell carcinomas of the oral cavity and oropharynx. The anatomic subsites treated include oral tongue (n = 29), floor of mouth (n = 22), base of tongue (n = 31) and tonsillar fossa (n = 20). Twenty-five patients (25%) had positive margins, 41 patients (40%) had close margins (< or = 0.5 cm from the surgical margin) and 36 (35%) had negative margins. The median radiation dose was 6000 cGy. RESULTS With a median follow-up of 7 years, the actuarial control rate for patients with positive, close and negative margins was 79%, 71%, and 79%, respectively. When postoperative doses of > or = 60 Gy were delivered to patients with positive/close margins (excluding patients with oral tongue lesions), the 7-year actuarial control was 92%. In similar patients receiving < 60 Gy, the actuarial control was 44% (p = 0.0007). Compared to other anatomic subsites, inferior control rates were obtained with oral tongue lesions. For this subsite, the control rates for positive, close, and negative margins were 50%, 62% and 69% respectively. CONCLUSION We conclude that excellent local control can be achieved with postoperative radiation therapy, despite the presence of inadequate margins of resection, when doses of > or = 60 Gy are used. Future strategies must be directed at further improving these results in patients with oral tongue lesions.

The effect of setup uncertainties on the treatment of nasopharynx cancer

PURPOSE As radiation treatment techniques become more complicated, the need to understand the effect of uncertainties on dose distributions increases. This study investigates the effect of positional uncertainities for patients with nasopharynx carcinoma treated with a multiple field conformal boost technique. Three dimensional setup errors were measured for six patients and the effect on patient dose was evaluated using dose volume histograms. METHODS AND MATERIALS A method is presented for determining 3-dimensional translational and rotational setup errors by identifying anatomical landmarks on two treatment field images and their corresponding simulation images. Measurements were made on a daily basis for six patients undergoing conformal treatment. RESULTS The average magnitude of the translational errors was between 1.5 and 3 mm while the average distance between simulation and treatment isocenters was 5 mm. Both systematic and random setup errors were observed. Dose volume histograms incorporating these uncertainties for standard parallel opposed and conformal techniques were generated for patients experiencing random and systematic setup errors. CONCLUSION The data imply that positional uncertainties effect the daily dose distributions for target and critical structures differently and that the effect may be treatment technique dependent. These results demonstrate the need to measure setup uncertainties for all sites and to develop techniques for incorporating dose uncertainties in treatment plans.

Concomitant chemotherapy-radiation therapy followed by hyperfractionated radiation therapy for advanced unresectable head and neck cancer

In January 1988, we initiated a prospective study evaluating a new treatment approach with chemotherapy and radiotherapy for unresectable head and neck cancer. Weeks 1-4 were the initial debulking phase. Radiotherapy was delivered using 1.8 Gy/day to large portals including gross disease and all areas at risk. Cisplatinum, 100mg/m2, was given concomitant with radiotherapy on days 1 and 22. Weeks 5 and 6 were the boosting phase. This involved twice-a-day irradiation. The AM fraction of 1.8 Gy was given to the entire area at risk, whereas the PM dose of 1.6 Gy was limited to the gross disease alone. Thus a total of 70 Gy/6 weeks was delivered. A total of 24 patients were treated, 22 of whom have completed this protocol and are evaluable. All patients had massive disease, with 15 having gross involvement of brain, orbit, skull base, or carotid artery. Follow-up ranged from 3-22 months (median 12 months). Major responses were achieved in 96%, with 64% complete responses and 32% partial responses. Two patients with PR were able to undergo complete surgical resection, making the overall rate of complete response, including surgery, 73%. At 1 year, actuarial survival was 69%, and local progression-free survival was 56%. Distant metastases developed in 5 (23%). This approach appears both safe and effective in producing excellent regression and local control for far advanced head and neck cancer. More time is needed to see if these results are sustained. Efforts to build upon this experience appear warranted.

Larynx Preservation with Combined Chemotherapy and Radiation Therapy in Advanced Hypopharynx Cancer

Twenty-five untreated patients with advanced, resectable squamous cell carcinoma of the hypopharynx, for whom standard treatment would have required total laryngectomy, were treated with one to three cycles of cisplatin-based chemotherapy with larynx preservation as the goal. Patients with a major (complete or partial) response to chemotherapy at the primary site were treated with definitive radiation therapy, with total laryngectomy reserved for salvage; patients with less than a partial response to chemotherapy had total laryngectomy and postoperative radiation therapy recommended. Four patients had a poor response to chemotherapy and thus were not candidates for laryngectomy. Total largynectomy was required for initial induction chemotherapy failure in five patients and for local recurrence in five others. Three additional patients had unresectable recurrence. Successful larynx preservation was achieved in 32% (8 of 25). With a median follow-up period of 41 months, the actuarial overall and failure-free 2-year survival rates were 44% and 32%, respectively. These preliminary data suggest larynx preservation is feasible in patients with advanced lesions of the hypopharynx. Improved local and regional control must be incorporated into the larynx preservation approach for hypopharyngeal lesions. A prospective, randomized study is necessary for a more valid comparison with conventional therapy, including comparative assessments of survival, morbidity, cost and functional results.

Effects of beam modifiers and immobilization devices on the dose in the build-up region

PURPOSE To analyze the effect that immobilization devices used in conjunction with beam modifiers may have on the dose to the skin and build-up region. METHODS AND MATERIALS Central axis depth dose measurements were made in a polystyrene phantom in the build-up regions using the 6 and 15 MV photon beams, at two different source-to-phantom distances, and various field sizes. The effects of acrylic blocking trays, lead wedges, and cerrobend blocks were assessed in conjunction with the enhancement of dose in the build-up region due to immobilizing devices using plaster and thermoplastic casting materials of different thicknesses. RESULTS For the 6 MV photons, solid (3 mm) thermoplastic casting material was found to have the greatest effect on surface dose: for a 12 x 12 cm field we measured 79% of maximum dose when treating through the material versus 22% of maximum dose when no beam modifiers or immobilization devices are used. Measurements were also made to evaluate the effect of the immobilization of patients receiving three-dimensional conformal treatments using a 15 MV photon beam. CONCLUSIONS The relevance of these results to treatments in the pelvis, breast, and head and neck regions is discussed. For 6 MV beams, special consideration should be given if the need arises to treat through the immobilization device, as unacceptable skin reactions may result.

Brachytherapy as part of the definitive management of squamous cancer of the base of tongue

Between 1981 and 1986, 17 patients were treated at the Department of Radiation Oncology at the Memorial Sloan-Kettering Cancer Center with squamous cancer of the base of the tongue whose definitive treatment included brachytherapy. The patient sample consisted of 14 men and 3 women with age range of 35 to 71 years (median = 58). There were four patients with T1 lesions, six with T2, six with T3, and one with T4. In general, treatment consisted of 5000-5400 cGy with external beam radiation and 2000-3000 cGy boost to the base of tongue via an Ir-192 implant using afterloading catheters. Necks were managed with elective radiation alone in the N0 group (n = 5) or with radiation plus neck dissection in the N+ group (n = 12). Five patients who would have required laryngectomy had they undergone primary surgery received neoadjuvant chemotherapy followed by external beam and implant as part of a larynx preservation study that was being done at our institution (4-T3, 1-T2). The range of follow-up is 8 to 59 months, with median follow-up of 24 months. No patients have been lost to follow-up. Crude local control by T-Stage are as follows: T1-4/4, T2-5/6, T3-5/6, T4-1/1. Actuarial local control at 24 months is 87%. There have been no neck failures. There have been five patients who had soft tissue ulceration (STU) and one patient who had osteoradionecrosis (ORN). All soft tissue ulceration patients have been successfully managed conservatively. The patient with osteoradionecrosis is currently being managed. In 4 of these 6 cases, the implant was the initial therapeutic intervention and the entire tumor bed was implanted. On the other hand, when external beam was the initial treatment, the boost was administered to the smaller volume of residual disease. Overall, 4 of 7 patients who had implant first developed either soft tissue ulceration or osteoradionecrosis, as opposed to 2 of 10 patients who had implant after external beam and/or chemotherapy. The numbers are too small to be statistically significant, but our current policy is to perform brachytherapy after the external beam. In addition, all those with either soft tissue ulceration or osteoradionecrosis were implanted with a non-looping technique. Overall, 6 of 12 patients treated with a non-looping technique developed an injury, whereas none of the five treated with a looping technique has developed one.(ABSTRACT TRUNCATED AT 400 WORDS)

Prospective computer-assisted voice analysis for patients with early stage glottic cancer: A preliminary report of the functional result of laryngeal irradiation

In January 1987 we began a prospective study aimed at evaluating objective parameters of vocal function for all patients treated with RT for early glottic cancer. All patients underwent vocal analysis using a voice analyzer interfaced with a computer. This allowed for the determination of percent voicing (%V) (normal = presence of phonation = 90-100%V). Other parameters such as breathiness (air turbulence or hoarseness) and strain (vocal cord tension) were also measured. Patients were recorded before RT, weekly during RT, and at set intervals after RT. There have been 25 patients studied. Eighteen (18) are evaluable at 9 months after treatment. All patients were male and ranged from 45-84 years old. Fourteen (14) and T1 lesions and received 66 GY/33 fractions to their larynx and 4 had T2 tumors and received 66-70 Gy/33-35 fractions. To date, all patients are locally controlled. Three distinct patterns of %V changes have been encountered. However, all patients demonstrated normal phonation pattern by 3 months after RT, and this is sustained at 9 months follow-up. In addition, 94% of patients have had significant decrease in breathiness after RT, which objectively documents diminished hoarseness. In 83%, breathiness is normal after RT. Most patients have had increased strain after RT, which documents increased vocal cord tension. However, strain remained within normal limits in 89%. Our preliminary analysis suggests that the majority of patients irradiated for early glottic cancer demonstrate a decrease in breathiness and an increase in strain after RT, and enjoy a resultant voice that has normal phonation maintained at 9 months after RT. Our data also demonstrate three distinct phonation patterns. Further follow-up will allow us to determine the prognostic significance, if any, of these patterns, and to continue to follow objective vocal parameters on larger numbers of patient.

Remote afterloading intraluminal brachytherapy in the treatment of rectal, rectosigmoid, and anal cancer: A feasibility study

From 1981 to 1986, 28 patients (27 evaluable) were treated with intraluminal brachytherapy (ILBT) using a remote afterloading technique for persistent or recurrent anal, rectal and rectosigmoid cancers. Eighty-nine percent underwent previous surgery for colorectal cancer. Seventy-seven percent of the patients received external beam irradiation (ERT) as a part of the present treatment. Intraluminal brachytherapy was given with a 2 cm diameter cylinder and the dose per fraction ranged from 440 cGy to 840 cGy at 0.5 cm from the surface of the cylinder. Follow-up ranged from 1 to 74 months with a median of 12 months. Patients were divided into two groups. Group I consisted of 15 patients receiving elective ILBT; Group II: 13 patients with recurrent disease. Seventy-one percent of the patients in Group I and 39% of the patients in Group II achieved local control. The majority of patients tolerated treatment well with only transient reactions. However, three patients (11%) developed grade 3 (G3) complications requiring surgical intervention. Eight patients developed moderate complications--grade 2 (G2)--requiring only conservative treatment. This study has identified several factors which appear to influence the risk of developing complications with this combined treatment, using remote afterloading apparatus, among which are technique of previous external beam irradiation, treatment length, anatomical location, intraluminal brachytherapy fractionation, and total cumulative dose (ERT + ILBT). This experience suggests that intraluminal brachytherapy appears to be an acceptable form of treatment, as a boost to external beam radiation therapy, in the management of rectal and colorectal cancers.