James E. Marks

Late effects of radiation therapy in the head and neck region.

The head and neck region is composed of numerous structures, each with an inherent response to radiation that is largely governed by the presence or absence of mucosa, salivary glands, or specialized organs within that site. Irradiated mucocutaneous tissues demonstrate increased vascular permeability that leads to fibrin deposition, subsequent collagen formation, and eventual fibrosis. Irradiated salivary tissue degenerates after relatively small doses, leading to markedly diminished salivary output. This, in turn, effects the teeth by promoting dental decay which, in turn, effects the integrity of the mandible. Details of these changes are presented, including their pathophysiology, clinical syndromes, and potential treatment.

Metastatic carcinoma in the cervical lymph nodes from an unknown primary site: results of bilateral neck plus mucosal irradiation vs. ipsilateral neck irradiation.

PURPOSE To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. METHODS AND MATERIALS Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. RESULTS Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p = 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. CONCLUSION Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective in controlling the ipsilateral neck disease.

IS PROPHYLACTIC NECK IRRADIATION INDICATED IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE MAXILLARY SINUS

PURPOSE To determine the proportion of patients with squamous cell carcinoma of the maxillary sinus who will fail in regional nodes without elective neck treatment and to identify any prognostic factors that may influence neck control. METHODS AND MATERIALS From 1971-1995, 42 consecutive patients with squamous cell carcinoma of the maxillary sinus were seen at our department for curative treatment. There were 35 males and 7 females, with a median age at diagnosis of 63.5 years (range, 42-77 years). One tumor was classified as T1, 5 had T2, 15 had T3, and 21 had T4 disease. Four of 42 patients (9.5%) had cervical lymphadenopathy at initial presentation. Thirty-three patients had surgical resection and radiotherapy and nine had radiotherapy alone. None of the 38 patients with clinical N0 necks received elective treatment to the cervical nodes. RESULTS Median overall survival was 30 months for all patients. Of the 38 patients with N0 disease, 11 (28.9%) had neck recurrence. Of the 11 neck failures, 9 were ipsilateral only, 1 was contralateral, and 1 had bilateral neck recurrence. The most common site of neck failure was in the upper neck (submandibular and jugulodigastric lymph nodes). Four of the 38 patients (10.5%) had isolated neck failure. Only tumor stage was found to be significant for neck relapse, with T1 and T2 doing worse compared to T3 and T4 tumors. Location of tumor (infrastructure vs. suprastructure), involvement of the oral cavity/oropharynx, nasal cavity, nasopharynx or orbit did not predict for cervical node relapse. Local control at the primary site was likewise not prognostic. The median overall survival for patients who remained N0 was 80 months and for those with initial cervical involvement or recurred in the neck without elective neck irradiation was 25 months (p = 0.05). CONCLUSION Based on the 28.9% rate of neck recurrence and the poor median survival of patients who recur in the neck, we recommend prophylactic ipsilateral neck irradiation in patients with T1-T4 squamous cell carcinoma of the maxillary sinus.

Effect of tumor bulk on local control and survival of patients with T1 glottic cancer

PURPOSE To evaluate the effect of tumor bulk in relation to various tumor-related prognostic factors and treatment-related variables on local control and survival of patients with T1 N0 M0 squamous cell carcinoma of the glottis. MATERIALS AND METHODS In 114 patients with T1 squamous cell carcinoma of the glottic larynx who were irradiated with curative intent, we determined the effect of tumor bulk in relation to mucosal extent (stage and anterior commissure involvement), histologic differentiation and various radiation factors, especially overall treatment time on local control and survival. Tumors were classified retrospectively as small surface lesions or bulky tumors. Seventy-seven patients had small lesions and 37 had bulky tumors. The anterior commissure was involved with cancer in 43 patients. The overall duration of irradiation ranged from 39 to 64 days. The median follow-up time was 6 years (range 5-24 years). RESULTS The 5-year actuarial local control rate for all patients was 82% after radiotherapy and 92% after salvage laryngectomy. On univariate analysis, bulky tumors and tumors involving the anterior commissure showed an adverse effect on local control, whereas the overall duration of irradiation had a borderline significance. The actuarial local control rate was 91% for small tumors and 58% for bulky tumors (P = 0.0002), 88% when the anterior commissure was not involved and 67% when the anterior commissure was involved (P = 0.01) and 89% when radiation was given in less than 50 days and 73% when irradiation exceeded 50 days (P = 0.06). On multivariate analysis. tumor bulk was the only significant factor that affected local control (P = 0.02). The 5-year actuarial survival for all patients was 73% and the disease-free survival was 92%. CONCLUSION This study shows that tumor bulk has a highly significant effect on the radiation control of T1 glottic cancer. Patients who had bulky tumors had lower local control and disease-free survival rates than those patients who had small tumors.

Childhood cerebellar astrocytomas : is there a role for postoperative irradiation ?

Eighty children with astrocytomas of the cerebellum were treated at Washington University Medical Center in St. Louis, Missouri from 1928-1980. The most important predictor of recurrence was completeness of surgical removal. Of 40 patients whose tumors were totally removed, only one recurred (2.5%). Forty cases were subtotally removed and 14 subsequently recurred (35%). Postoperative irradiation did not significantly improve survival in the patients with incompletely excised tumors; however, there was lack of uniformity in the radiation therapy. Although a survival advantage could not be demonstrated, there was a trend toward a lowering of the recurrence rates in patients with subtotally excised solid tumors who received radiation therapy.

Parotid-sparing irradiation for cancer of the oral cavity: Maintenance of oral nutrition and body weight by preserving parotid function

&NA; The purpose of this study was to assess the nutritional benefit of parotid‐sparing irradiation, comparing the body weights of patients irradiated with parotid‐sparing technique versus those irradiated with bilateral opposed photon beams, including both parotid glands in the radiation fields. One hundred fourteen patients with cancer of the oral cavity were irradiated with curative intent. Two‐dimensional radiotherapy techniques sparing at least one parotid gland from the radiation beams were used to treat 31 patients (parotid‐sparing techniques). Eightythree patients were irradiated using bilateral opposed photon beams, which included both parotid glands (bilateral technique). Body weight during and after irradiation, treatment outcome, and survival were compared. Patients treated with parotid‐sparing techniques maintained their nutritional intake and baseline body weight during and after irradiation. Patients treated with the bilateral technique that included both parotid glands had poor nutritional intake, leading to a more than 10% decline in their initial body weight; these patients did not regain their body weight during the 2‐year follow‐up period. Primary tumor control rate was higher for patients treated with parotidsparing techniques than for patients who had both parotid glands irradiated (70% versus 48%; p = 0.05). This difference is because a higher percentage of patients treated with parotidsparing techniques had early‐stage tumors (54%) compared with patients treated with the bilateral technique (24%). When analyzed according to the tumor stage, the primary tumor control rates for patients treated with parotid‐sparing techniques and for patients treated with the bilateral technique showed no difference; control rates were 93% and 87% (p = 1.00) for early‐stage tumors and 42% and 36% (p = 0.75) for advanced‐stage tumors, respectively. Nodal control rates in the ipsilateral side of the neck and in the contralateral side of the neck for patients treated with parotid‐sparing techniques and with the bilateral technique were not significantly different— 74% versus 76% (p = 0.86) and 70% versus 82% (p = 0.21), respectively. Sparing at least one parotid gland during irradiation of patients with head and neck cancer will preserve parotid function and prevent xerostomia. Patients treated with parotidsparing techniques were able to maintain their oral nutrition and body weight, compared with patients who had both parotid glands irradiated. A higher percentage of patients treated with parotid‐sparing techniques had early‐stage tumors, resulting in higher rates of primary tumor control and survival in this group of patients.

Treatment of locally advanced, high-grade, malignant tumors of major salivary glands.

A retrospective review of 45 patients with Stage in and IV malignant tumors of the major salivary glands was undertaken to determine tumor control and patient survival after treatment with surgery and conventional ionizing‐radiation therapy. Eight of the 23 patients received early postoperative radiotherapy after initial surgical resection, with a local control rate of 75%. Twelve of 23 patients had surgery as definitive treatment and the tumor recurred locally in all; seven of these 12 patients were subsequently salvaged by further surgery plus postoperative radiotherapy or by radiotherapy alone, with 58% ultimate local control. The remaining three patients had unresectable tumors at diagnosis and received radiation alone, with a local tumor control rate of 33%. Patients were also analyzed according to the extent of surgical resection prior to radiation therapy and according to radiation dose. Eighty‐eight percent of completely resected, 50% of partially resected, and 44% of unresected tumors were locally controlled for an overall local control rate of 61%. The 5‐year survival rate was significantly higher for patients with local tumor control than for patients who failed locally (31% vs. 0%).

Total atelectasis of the lung secondary to malignant airway obstruction : response to radiation therapy

From 1980 to 1986. 48 patients with bronchogenic carcinoma were diagnosed to have total atelectasis of the lung as a result of tumor obstructing the mainstcm bronchus. These patients were treated with external beam radiotherapy with doses ranging from 30 to 60 Gy given in 2–6 weeks. Bronchial obstruction was relieved in 74% of patients, resulting in complete or partial reexpansion of the lung. Seventy-one percent of patients irradiated within 2 weeks after radiological evidence of atelectasis had complete reexpansion of their lungs, whereas only 23% of those irradiated after 2 weeks showed a similar response. Atelectasis recurred in 12% of those who initially responded to radiation therapy with complete or partial reexpansion.

Postoperative Irradiation of Patients with Malignant Tumors of the Skull Base

To better understand how to irradiate patients after skull‐base surgery, the authors of this study analyzed the tumor recurrence patterns in 22 patients with various malignancies. Of these patients, 13 underwent craniofacial resection, 6 had infratemporal fossa resection, and 3 had temporal bone resection. The entire operative field was irradiated in 8 patients (total‐field group), and part of the operative field was irradiated in 14 patients(partial‐field group).

Radiotherapy alone compared with radiotherapy and chemotherapy in patients with squamous cell carcinoma of the esophagus.

PurposeThe purpose of this study is to determine whether primary treatment with both radiotherapy and chemotherapy is superior to radiotherapy alone in patients with squamous cell carcinoma of the esophagus. Patients and MethodsFrom January 1980 to December 1988, 77 patients from two Veterans Affairs hospitals with clinically staged nonmetastatic squamous cell carcinoma of the esophagus received either radiotherapy alone (RT group) or concomitant radiotherapy and chemotherapy (RT + CT group) with curative intent. Each group originated at a different hospital, but all patients were irradiated in the same radiotherapy department. Chemotherapy consisted of cisplatin and 5-fluorouracil. Forty-two patients received RT alone, and 35 received RT + CT. Locoregional control, disease-free survival, and overall survival rates were compared. ResultsLocoregional control, disease-free survival, and overall survival rates were significantly higher in the RT + CT group when compared to RT group, 26% vs 5%, 20% vs 2%, and 29% vs 7%, respectively, at 2 years (P = .01, 0.02 and 0.02, respectively). The median survival was 14 months for the RT + CT group and 7.5 months for the RT group. There was no difference in the incidence of distant metastases except for bone metastases. No one in the RT + CT group developed bone metastases compared to nine patients in the RT group (P = .01). Conclusion: This retrospective analysis shows improved locoregional control, disease-free survival, and survival when chemotherapy consisting of cisplatin and 5-FU is given in addition to radiation for patients with squamous cell carcinoma of the esophagus. Bony metastases were absent in those who received chemotherapy.