Distribution Of Primary Sites Research Articles

Evaluating the hidden biology of cancer of unknown primary (CUP) in comparison to known metastatic disease.

e12549 Background: No consensus exists yet on whether CUP is a group of metastatic tumours with undetected primary sites or a unique clinicopathological entity with distinct genetic and phenotypic characteristics. We aimed to characterize the clinical and pathologic features of a cohort of CUP patients who had their latent primary site subsequently detected during their life or at autopsy in comparison to a cohort of patient presented with metastatic known primary cancers at initial diagnosis. Methods: We used historical snapshot files available in the Manitoba Cancer Registry (MCR) to identify all patients diagnosed with histologically or cytologically confirmed metastatic tumours in Manitoba during the period from January 1, 2002 to December 31, 2012. We linked all identified patients with their updated tumour-specific files available in the MCR for the purpose of identifying our two study cohorts. The first cohort included all patients who were initially diagnosed with CUP and who had their latent primary cancer identified and confirmed using either histology, cytology or autopsy at least 2 months after their initial CUP diagnosis. The second cohort included all patients initially diagnosed with a metastatic known primary cancer and whose cancer diagnosis did not change during lifetime or at autopsy. Information on patient and tumour characteristics was obtained from the MCR. Results: Out of 16,085 patients diagnosed with metastatic tumours, 2654 (%16.5) patients were initially diagnosed with CUP and 13,431 (84.5%) patients diagnosed with metastases of a known primary cancer. Out of the CUP group, 1033 (39%) patients had their latent primary site subsequently detected. Distribution of primary sites did not differ significantly between CUP patients who had their latent primary detected and patients diagnosed with metastases of a known primary cancer (p=0.44, Wilcoxon rank sum test). With the exception of tumour size, all other patient and tumour characteristics did not differ significantly between the two study cohorts across primary tumour sites. Conclusions: The clinical and pathologic features of CUP patient do not appear to be fundamentally different from those with metastatic known primary cancers.

Clinical features, presentation, and tolerance of platinum‐based chemotherapy in germ cell tumor patients 50 years of age and older

Germ cell tumors (GCTs) primarily affect adolescent and young adult men. Detailed clinical and treatment characteristics in older men are lacking. Patients with GCT seen over a 20-year period at Memorial Sloan-Kettering Cancer Center were identified. Primary tumor site and histology were compared for patients aged ≥ 50 years at diagnosis versus younger men. For patients aged ≥ 50, individual chart review was performed and treatment delays, changes, and toxicities were recorded for those treated with first-line chemotherapy. Of 4235 diagnoses of GCT, 3999 (94.4%) were made at age < 50 versus 236 (5.6%) at age ≥ 50. Compared with patients diagnosed before age 50, older men more frequently had seminoma (62.7% versus 36.7%) and less frequently, nonseminoma (34.7% versus 63.2%) (P < .0001). Predominant histology switched from nonseminoma to seminoma around age 35. Distribution of primary sites also differed for older versus younger men (testis: 89.4% versus 92.9%; retroperitoneal: 3.8% versus 0.7%; CNS 0% versus 1.7%) except for mediastinal primary tumors, which remained constant across age groups. Fifty patients age ≥ 50 received first-line platinum-based chemotherapy; 30 experienced complications leading to treatment discontinuation, delay ≥ 7 days, or regimen change. Twenty-two (44%) patients experienced neutropenic fever, 6 despite prophylactic growth factor support. Estimated 5-year survival for chemotherapy-treated patients was 84.9%. Men aged ≥ 50 years comprise less than 10% of GCT diagnoses and have distinct clinical and histological characteristics as compared with younger patients. Although complications from chemotherapy occur frequently in older men, prognosis remains excellent when risk-directed treatment is administered with curative intent.

Role of extracorporeal irradiation in malignant bone tumors

Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en-bloc removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation, and re-implantation back in the body. We report our preliminary experience of using ECI for management of MBT. From year 2009 to 2010, 14 patients with primary MBT were enrolled into this study. The eligibility criteria included histopathological proof of malignancy, no evidence of distant metastases, and suitability for limb preservation therapy. Surgery was performed about 4 weeks after completion of neoadjuvant chemotherapy. The affected bone segment was resected, irradiated extracorporeally with a dose of 50 Gy and reimplanted. Local control, complications and short-term survival were studied. Functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system. There were 10 males and four females with median age of 14 years. Histopthologically, nine patients had osteosarcoma (OS) and five had Ewing's sarcoma family of tumors (ESFT). Distribution of primary site was as follows: Femur eight patients, tibia five patients and humerus one patient. At a median follow-up was 22 months, three patients (two OS, one ESFT) had local recurrence. Two patients (14%) developed wound infection in the perioperative period. The 2 year local recurrence free survival was 73% and mean MSTS score was 88. Results of our study suggest that ECI is technically feasible in the management of MBT and provides decent local control and short-term survival rates.

Ossifying fibroma of the jaws: a clinical study of 14 cases and review of the literature

The purpose of this study was to evaluate the clinical outcomes of ossifying fibroma (OF) in a group of 14 patients treated in our clinic and discuss the management and the prognosis of this tumor. The study included 14 consecutive patients with OF of the jaws with ages ranging from 7 to 55 years. Primary site distribution was maxilla (1), maxilla, maxillary sinus (1), and mandible (12). All of the patients treated by surgery (curettage, enucleation, or radical surgery). The mean follow-up range was 2-18 years. All of the patients were alive and disease free. OF is a benign slow-growing tumor of the jaws. Early tumors that are small or well demarcated are treated by curettage or enucleation. For aggressive tumors that show rapid enlargement, radical resection (maxillectomy or segmental mandibulectomy) is used. By either method of treatment, the recurrence rate is extremely low.

A GEP-NEN analysis of incidence, ethic variation, and mortality using the SEER database.

225 Background: A decade of epidemiological analysis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has defined this malignancy as more common than previously recognized, but the cause of an apparent increase in incidence is controversial. The maturity of the contemporary SEER17 database allows this issue to be addressed. Methods: We analyzed the most recent SEER17 database (including 32,862 cases of GEP-NEN) to calculate incidence, primary site distribution and survival (cause-specific and all-cause) by age and ethnicity in 2000 to 2008, then examined 20-year limited-duration prevalence and the pattern of second cancer risk. Results: The incidence of GEP-NENs continues to rise (APC; 4.2% per year) and is now 3.6/100,000 but this reflects an improved diagnostic acuity rather than a true increase in disease occurrence. Of paramount import, the prevalence of GEP-NENs (23/100,000) accounts for only approximately 2% of the prevalence observed in autopsy studies (1,110/100,000), providing the necessary perspective to recognize the change in incidence as “trivial” relative to the undiagnosed disease burden. The current analysis also reminds us that GEP-NENs are not uniformly fatal. Cause-specific GEP-NEN survival is considerably more favorable than the commonly described ‘all-cause’ survival, so that many patients with rectal (62%), gastric (49%), small intestinal (44%), appendiceal (24%), and colonic (19%) NENs died from other causes. The high proportion of rectal primaries in Japan (56%) persists after population migration to the US (65%), suggesting a “relatively” stable inherited predisposition. The risk of second cancers after GEP-NENs is increased by 55% and occurs in organs with epithelium that contain neuroendocrine cells (both GI and distant), not limited to the luminal sites potentially exposed to a dietary carcinogen. Conclusions: The increase in GEP-NEN incidence is illusory, disease specific survival is higher than previously recognized while the stable ethnic differences and systemic second cancer risk support a non-environmental genetic etiology for tumorigenesis.

Surgery Alone or Combined with Postoperative Radiotherapy for Adenoid Cystic Carcinoma of the Head and Neck

Surgery Alone or Combined with Postoperative Radiotherapy for Adenoid Cystic Carcinoma of the Head and Neck

Role of videofluorography in assessing functional abnormalities in patients of head and neck cancer treated with chemoradiotherapy

Aim: The major toxicity following treatment for head neck cancer is swallowing dysfunction which can be easily assessed by videofluorography (VFG), allowing documentation of the site and extent of abnormality thereby facilitating directed management. Methods: Between October 2003 and January 2007, 56 patients with locally advanced head and neck cancer were treated by an accelerated radiotherapy schedule with concurrent weekly cisplatin chemotherapy. Three months following treatment, these patients were locally disease free clinically, but complained of varying degrees of dysphagia and were subjected to a VFG evaluation. Results: This group comprised 52 men and four women with a median age of 56 years. The primary site distribution was: oral cavity (9), oropharynx (22), larynx (19), hypopharynx (5) and unknown primary (1). Swallowing function abnormalities in the form of structural displacement and temporal delays were documented and recorded as weakness of the tongue musculature (n = 6), palatal kink (n = 8), premature leak into the oropharynx (n = 20), impaired hyoid elevation (n = 23), impaired epiglottic tilt (n = 26), unilateral pharyngeal wall impairment (n = 16), residuum in vallecula or pyriform fossa (n = 30), aspiration in trachea (n = 29) and loss of nasopharyngeal seal (n = 7). Multiple abnormalities of different sub-sites were seen in each patient. Conclusion: VFG can document dysmotility disorders of upper aero-digestive tract like dysfunction of the base of tongue, larynx and pharyngeal musculature leading to stasis of the bolus and vallecular residuum, epiglottis dysmotility resulting in silent aspirations, and inadequate nasopharyngeal seal leading to nasal regurgitation. A clinical correlation alongwith quantification of VFG findings is required.

A Retrospective Analysis of Concurrent CRT in HNSCC Cases using Low Doses of CDDP: Efficacy of Combination with Hybrid Type AHF only Indicated during Chemotherapy

To evaluate long term results on survival, locoregional control and larynx preservation in the patients with operable Stage III–IV laryngopharyngeal Ca mainly, who had been treated with low-dose of CDDP regimen. To evaluate an altered fractionated RT regimen in which AHF was indicated only during 2 cycles of chemotherapy, which was introduced in order to intensify RT more than conventional schedule. Since April 1992 to March 2007, 102 cases with loco- regional advanced but operable laryngopharyngeal SCC has been consecutively treated with 2 cycles of chemotherapy, Chemotherapy regimen was 20mg/m2 4 times a week of CDDP or CDGP. CDGP was administered in patients with low renal function (CCr24<70ml/min) or adverse effects after first course of CDDP. Since April 1999, 71 patients has been consecutively enrolled to the hybrid type AHF regimen which was indicated in only chemotherapy weeks. 1.5 Gy/F b.i.d. 4 days a week was administered in first and 5th week of total 6.5 weeks RT schedule. They were compared with another group of 31 cases treated in 7.5 weeks conventional schedule before the altered fractionation regimen started. Prescribed doses of hybrid type AHF and conventional schedule were 68 Gy/36F/6.5 weeks and 68.2 Gy/31F/7.5 weeks, respectively. The BED at α/β=10 for each them were 56.5 and 58.7, respectively, and at α/β=3 they were 104.6 and 118.2, respectively. As primary site distribution was unbalanced between two groups, we also analyzed for primary adjusted 73 cases with oropharynx T4 limited, hypopharynx, and larynx. Finally the distribution became 1: 22: 8 in the former and 2: 30: 10 in the latter. The Stage distribution on Stage II: III: IVA was 5: 14: 12 in the former and 6: 14: 22 in the latter, respectively, in the 73 cases. Median observation time was 92 months in the conventional group and 35 months in the hybrid AHF group. Eighteen cases of all had experienced double cancer and 2 cases triple. Five-year CSS was 80.6% in the former, 90.2% in the latter. Definitive RT were done in 94 cases of all. In primary adjustment study 5-year CSS was 80.6% in the conventional group, and 89.2% in the hybrid type AHF (p = 0.235), 5-year locoregional RFS was 86.3% and 86.7%, respectively. And 5-year larynx preservation rate was 73.3% and 92.7%, respectively. There was significant difference between two groups (p = 0.028) only in the larynx preservation rate. We have experienced CRT using low dose CDDP/CDGP for 102 cases with locally advanced but operable HNSCC for 15 years. From this historical control analysis we estimate that CRT combination with hybrid type AHF would make functional preservation easier than CRT in conventional schedule in operable HNSCC. We should make a plan for the RCS on this issue as soon as we can.

Multicentric Prospective Study on the Prevalence of Sublevel IIB Metastases in Head and Neck Cancer

To evaluate the prevalence of sublevel IIB lymph node (LN) metastases for head and neck primary tumors in a large cohort of patients. Prospective study. One referral university hospital and 2 national institutes of oncology. Between 2003 and 2005, 297 patients (male to female ratio, 3.5:1; mean age, 58.8 years [range, 18-89 years]) affected by head and neck cancer were treated by surgery on the primary tumor and/or the neck. Primary site distribution included the following: oral cavity in 111 patients, larynx in 92, oropharynx in 32, thyroid gland in 22, skin of the lateral face or scalp in 16, hypopharynx in 11, unknown primary in 7, and parotid gland in 6. Sublevel IIB was evaluated for the number of LNs and pathologic N (pN) status. All patients underwent unilateral or bilateral neck dissection (ND) with therapeutic or elective intent according to the primary site and clinical T (cT) and clinical N (cN) status. Sublevel IIB was selectively dissected at the beginning of ND, labeled, and processed independently. The distribution of metastases among the different levels was analyzed. The influence of several factors (institution in which the surgical procedure was performed, sex of the patient, site of primary, histotype, pathologic T [pT] status, cN status, lower level involved in the neck together with sublevel IIB, association with sublevel IIA metastasis, ipsilateral number of involved levels, and previous surgical treatment limited on the primary site) on the prevalence of sublevel IIB metastasis was statistically evaluated by the Pearson chi(2) test or Fisher exact test. A total of 443 NDs were performed (unilateral in 151 patients and bilateral in 146). Among the patients, the tumors were staged cN0/pN0 in 27%, cN+/pN+ in 50%, cN+/pN0 in 7%, and cN0/pN+ in 16%. The mean number of LNs collected at sublevel IIB was 5.4 (range, 0-24). The overall prevalence of sublevel IIB metastases was 5.6% (26 neck sides). Tumor histologic type in the sublevel IIB+ population was squamous cell carcinoma in 80%, papillary carcinoma in 8%, melanoma in 8%, and adenocarcinoma in 4%. The chi(2) test showed a significantly higher risk for LN metastases at sublevel IIB in patients affected by parotid gland primary tumors (33%), tumors of the skin or scalp (25%), unknown primary tumors (14%), and cancers of the oral cavity (10%) (P = .02) and in those clinically staged as cN+ (P < .001). Sublevel IIB dissection is strongly recommended for all patients with cN+ tumors and in those affected by tumor of the parotid gland, skin, and scalp scheduled for elective ND. Patients affected by laryngeal cancer scheduled for elective ND can be considered the ideal candidates for preservation of sublevel IIB. However, whether this policy could be associated with a better functional outcome remains to be demonstrated by prospective studies on a large series of patients.

Malignant melanoma in Chile: an unusual distribution of primary sites in men from low socioeconomic strata

Mortality from malignant melanoma (MM) has increased in Chile in the past decade. The location of MM lesions on the body has been correlated with prognosis and survival. To review body site and gender relationships with histopathologically confirmed primary MM in Chile. Records of 575 cases presenting to 5 state hospitals from 1992 to 2001 were analysed. There were 360 women and 215 men. Women showed a significantly higher number of MM on the legs, cheeks and arms, and in the genital area, whereas men showed a significantly higher number on the ears, backs of the hands, soles and feet. Men had a predilection for MM with a poor prognosis. The different body site distribution of primary MM in men and women may be explained by a different pattern of sun exposure. Ethnic and genetic factors may also be involved. The predominant location of MM in women in Chile is similar to white populations, whereas the location in men is similar to that observed in black and Asian populations. These observations may be relevant to the high mortality of MM in Chilean men.

Treatment of non-metastatic rhabdomyosarcoma and other non rhabdomyosarcoma soft tissue malignant tumours of childood and adolesence

8557 Background: At NCI Egypt, soft tissue sarcomas represent 3.75% of total malignancies & 27.6% of these occur in pediatric age group. Rhabdomyosarcoma (RMS) is the most common type. Methods: This work is a prospective study including 56 children and adolescents, aged 21 years or less treated by upfront chemotherapy and local treatment by surgery or radiotherapy or both after assessment of tumor response at week 9. Children were categorized according to the site, size, type of surgery into 3 risk groups. 54 children received the high risk regimen of chemotherpy consisted of alternating 6 drugs (Ifosfamide 6gm/m2, Adriamycin 75mg/m2, Vincristine 1.5mg/m2, Carboplatin 500mg/m2, Actinomycin-D 1.5m/m2, Etoposide 200mg/m2) for 9 courses. Results: The distribution of primary site of study group was orbit 12.5%, parameningeal sites 12.5%, other head & neck sites 10.7%, extremity 28.6%, trunk 12.5%, bladder & prostate 7.1%, retroperitoneal 7.1% & others 7.2%. The majority of children presented with tumor size more than 5 cm. in 72.5%. Among children with RMS 62% were embryonal, 27% were alveolar. At w 9 evaluation of tumor response revealed 43% complete response, 46% good partial response, 7% partial response, while 2% stationary disease & one child died. The OAS & DFS for the whole group was 73% ± 9%, & 53% ± 9% respectively with a median follow up period of 24 months. Sixteen children relapsed, 7 locoregional, 6 distant failure & 3 chidren both. The DFS was significantly affected by tumor size 93% ± 6% for tumors < 5 cm. versus 42% ± 10% for those >5 cm., P value of 0.03. The local failure free survival was 61% ± 13%. It was significantly affected by the administration of radiotherapy (94% ± 4% for patients received radiotherapy versus 58% ± 15% for those wo did not receive radiotherapy, P=0.02). On multivariate analysis radiotherapy was a significant factor with a P value of 0.04. Regarding the treatment toxicity, one patient died of fungal pneumonia. Conclusion: Chemotherapy regimen used for this study (high risk 54 children out 56) was well tolerated with one mortality. Radiation therpy is effective modality but it should be refined to reduce its late sequale by the use of IMRT & brachytherapy. No significant financial relationships to disclose.

Double-blind, randomized trial of granulocyte-colony stimulating factor (GCSF) versus (v.) placebo during postoperative radiation (RT) for advanced resectable squamous cell head and neck cancer (SCCHN): Impact on mucositis

5587 Background: Mucositis is common in patients (pts) with SCCHN receiving RT, contributing to the need for tube feeds (PEG) and treatment delays. GCSF has decreased mucositis in pts receiving chemotherapy (CT). We evaluated its ability to decrease mucositis and related dysfunction during postoperative RT using a randomized, placebo-controlled design. Methods: Eligible pts had completely resected, stage II-IV SCCHN, no prior RT or CT, and signed informed consent. Pts were stratified by primary site, then randomized to receive GCSF 3 mcg/kg or placebo daily by subcutaneous injection during RT (63 Gy, 1.8 Gy/day). Pts and treating physicians were blinded to treatment assignment. Endpoints: need for PEG feeds (primary), severity of mucositis/level of intervention for mucositis (secondary; both scored biweekly, grades 0–3). Results: 41 pts (132 planned) were enrolled at MSKCC from 1/92 to 12/96. Study was closed due to slow accrual. Pt characteristics (GCSF v. placebo): median age 59 v. 54; pathologic stages: T3/4 32 v. 50%, N2/3 68 v. 59%, Stage IV 79 v. 68%. Primary site distribution was comparable between groups. All pts Karnofsky ≥ 80. Mean absolute neutrophil count during RT 24.1 v. 4.1 x109/L (p<0.0001). 9 pts treated with GCSF required dose reduction (white blood count ≥ 40 x109/L, radiotherapist blinded), 2 pts had grade 2/3 bone pain, 3 pts total refused injection (2 GCSF, 1 placebo). 39 pts were evaluable. All received 63 Gy. Outcomes (GCSF v. placebo): PEG rate 0 v. 10% (p=0.16), RT interruption 0 v. 10% (p=0.16), mean mucositis grade 0.84 v. 1.11 (p=0.11), mean level intervention 0.59 v. 0.95 (p=0.076), mean # of treatment days 35.9 v. 38.1 (p=0.007). 5-year actuarial survival (intent to treat, 41 pts, median followup 7.6 years) was 79 v. 47% (p=0.062, log rank test). Conclusions: GCSF during RT was feasible, led to trends for less PEG feeds and mucositis (underpowered), significantly less # of treatment days, and no decrement in survival. Survival data are not clearly explained by known prognostic factors, and warrant further study. No significant financial relationships to disclose.

Radiation therapy for early-stage carcinoma of the oropharynx

Purpose To evaluate the outcomes of radiation therapy treatment of patients with Stage I and II squamous cell carcinoma (SCC) of the oropharynx and discover adverse prognostic factors that may help select a subgroup of patients for a different management approach. Methods and materials A search of the database maintained by the Department of Radiation Oncology of The University of Texas M. D. Anderson Cancer Center for patients with Stage I or II SCC of the oropharynx was performed. This search identified 175 patients treated between 1970 and 1998 who met the inclusion criteria for this retrospective study. Distribution of primary sites was: tonsillar fossa/pillar, 60 patients; soft palate, 55 patients; base of tongue, 40 patients; and pharyngeal wall, 20 patients. Twenty-five patients were stage T1, 124 were T2, and 26 were Tx. All patients were treated with fractionated radiation to a median dose of 66 Gy. Eighty-five patients were treated with conventionally fractionated radiation, 73 were treated with the concomitant boost fractionation schedule, and the remaining 17 were treated with other altered fractionation schedules or with intraoral or interstitial boosts. Results The median follow-up for all patients was 76 months (range, 2–302 months). The actuarial 5-year local control (LC), regional control, locoregional control (LRC), and disease-free survival (DFS) rates were 85%, 93%, 81%, and 77%, respectively. Only 7 patients (5%) with LC developed nodal metastases, and 10 patients (7%) with LRC developed distant metastases. Eleven patients (32%) with locoregional recurrence were rendered without evidence of disease after a surgical salvage procedure, resulting in a 5- year ultimate LRC rate of 87%. T-stage classification was statistically significant ( p = 0.03) in univariate analysis for actuarial 5-year LRC, 88% for Stage I vs. 72% for Stage II. The 5- and 10-year disease-specific survival rates were 85% and 79%, respectively, while the actuarial 5- and 10-year overall survival rates were 70% and 43%, respectively. Fifty-one patients (29%) developed second primary tumors, 86% of which were cancers of the upper aerodigestive tract (UADT). Heavy alcohol consumption was associated with both an increased risk of disease recurrence and development of a second cancer of the UADT. Conclusions Patients with early-stage oropharynx cancer have high rates of disease control when treated with radiation. Lymphatic and hematogenous metastases are uncommon. Surgical salvage of disease recurrence is successful in approximately one-third of patients. As the majority of recurrences occur within the first 2 years from treatment, close observation during this time period is important. The development of second primary tumors of the UADT adversely impacts survival in these patients to as great a degree as the index cancer.

An analysis of first-time enquirers to the CancerBACUP information service: variations with cancer site, demographic status and geographical location.

A retrospective comparison of cancer incidence data and, where relevant, population data with 16 955first-time users (patients, relatives and friends) of a national cancer information service (CancerBACUP) during the period April1995 to March 1996 is presented. The number of events observed was compared with the number of events expected, were the nationalrates of cancer incidence and population demographics apply. Standardized incidence ratios (SIRs) (observed – expectedratios) were used to indicate any differences. Statistically significant differences (P< 0.001) in the observed andexpected sex, age and primary site distribution of patients enquired about were found. Statistically significant differences(P< 0.001) were also identified for the age, employment status, socioeconomic class and geographical location offirst-time enquirers (patients, relatives and friends). Enquiries about brain, testis and breast cancers and non-Hodgkin'slymphoma (NHL) were substantially higher than expected; enquiries about bladder, lung, stomach and colorectal cancers were muchlower than expected. As the service is provided via a freephone number, it is available to all, and users might be expected to berandomly distributed across the variables listed. The underlying reasons for the differences identified need to be investigated,and the role of information in the care of cancer patients should be formally evaluated. © 1999 Cancer Research Campaign

The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation

Surgery is the primary treatment for adenoid cystic carcinomas arising from major and minor salivary glands of the head and neck. However, local recurrence is frequent because of the infiltrative growth pattern and perineural spread associated with these tumors. At UTMDACC, we have had a longstanding policy of using postoperative radiotherapy to reduce the risk of local recurrence and to avoid the need for radical surgery; this 30-year retrospective study analyzes the results of this combined modality approach. Between 1962 and 1991, 198 patients ages 13-82 years, with adenoid cystic carcinomas of the head and neck, received postoperative radiotherapy for known or suspected microscopic residual disease following surgery. Distribution of primary sites was: parotid: 30 patients; submandibular/sublingual: 41 patients; lacrimal: 5 patients; and minor salivary glands: 122 patients. Eighty-three patients (42%) had microscopic positive margins and an additional 55 (28%) had close (< or = 5 mm) or uncertain margins. One hundred thirty-six patients (69%) had perineural spread with invasion of a major (named) nerve in 55 patients (28%). Using radiation techniques appropriate to the primary site, a median dose of 60 Gy (range 50-69 Gy) was delivered to the tumor bed. Follow-up ranged from 5-341 months (median, 93 months). All surviving patients had a minimum of 2 years follow-up. Twenty-three patients (12%) had local recurrences with 5-, 10-, and 15-year actuarial local control rates of 95%, 86%, and 79%, respectively. Fifteen of the 83 patients (18%) with positive margins developed local recurrences, compared to 5 of 55 patients (9%) with close or uncertain margins, and 3 of 60 patients (5%) with negative margins (p = 0.02). Patients with and without a major (named) nerve involved had crude failure rates of 18% (10 out of 55) and 9% (13 out of 143), respectively (p = 0.02). There was a trend toward better local control with increasing dose. This was significant in patients with positive margins, in whom crude control rates were 40 and 88% for doses of < 56 Gy and > or = 56 Gy, respectively (p = 0.006). Actuarial 5-, 10-, and 15-year freedom from relapse rates were 68%, 52%, and 45%, respectively. Base of skull and neck failures were uncommon with or without elective treatment, developing in 2 and 3% of patients, respectively. Distant metastases were the most common type of disease recurrence, developing in 74 patients (37%) of whom 62 (31%) were disease-free at the primary site. Excellent local control rates were obtained in this population using surgery and postoperative radiotherapy and we recommend this combined approach for most patients with adenoid cystic carcinomas of the head and neck. Perineural invasion was an adverse prognostic factor only when a major (named) nerve was involved. Microscopic positive margins was also an adverse prognostic factor, but even when present, local control was achieved in over 80% of our patients. We recommend a dose of 60 Gy to the tumor bed, supplemented to 66 Gy for patients with positive margins. Despite effective local therapy, one-third of patients fail systemically, and good treatment to address this problem is lacking.

Ewing's sarcoma metastatic at diagnosis results and comparisons of two intergroup Ewing's sarcoma studies

Two Pediatric Intergroup Ewing's Sarcoma studies of patients with metastatic disease (IESS-MD) have used multimodal therapy consisting of intensive combination chemotherapy and radiation therapy (XRT) to areas of gross disease detected at the time of diagnosis. In IESS-MD-I, conducted from 1975 to 1977, 53 eligible patients were entered and received the chemotherapeutic agents vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and dactinomycin with concomitant XRT (VACA + XRT). In IESS-MD-II, conducted from 1980 to 1983, 69 eligible patients were entered and received 5-fluorouracil (5FU) in addition to the chemotherapeutic agents of IESS-MD-I; initial intensive chemotherapy was given and XRT was delayed until week 10 (VACA + 5FU, delayed XRT). The best response rate (complete and partial remissions combined) was 73% in IESS-MD-I and 70% in IESS-MD-II, so there was no statistical evidence of a difference in response rates (P = 0.62). The length of best response also was similar between studies (P = 0.79), with approximately 30% of the patients on both studies remaining in remission at 3 years. The percentage of patients surviving 5 years or more was 30 on the first study and 28 on the second study (P = 0.49). The major sites of relapse after a response were lung and bone, each occurring with nearly equal frequency. The age of the patient was related to both best response rate and survival: patients 10 years of age or younger had substantially higher response and survival rates than patients 11 years of age or older. The favorable prognosis for younger patients might be explained by a more favorable distribution of primary sites at diagnosis; 39% of patients 10 years of age or younger had rib primary sites, compared with only 16% for patients older than 10 years of age (P = 0.05). The frequency of life-threatening toxicity was substantially higher in IESS-MD-I (30%) than in IESS-MD-II (9%), but the frequency of fatal toxicity was similar (6% to 7%). Fatal complications included Adriamycin-induced cardiomyopathy, Pneumocystis carinii pneumonia, unspecified pneumonitis, and sepsis. The most common toxicity and complications were leukopenia and infections.

Brain metastases: results and effects of re-irradiation.

Re-irradiation for recurrent manifestations of brain metastases has been reported to be of benefit by either increasing the duration of survival or improving the quality of life. The records of 455 patients with brain metastases treated by radiation therapy at the University of Colorado Health Sciences Center from 1975 through 1986 were reviewed. Of these, 44 patients (9.7%) were re-irradiated because of suggestive neurological findings and/or imaging studies diagnostic of recurrent disease. The primary site distribution was as follows: lung (non-small cell)--15 (34%), lung (small cell)--9 (20%), melanoma--5 (11%), breast--4 (9%), genitourinary--4 (9%), unknown--4 (9%), lymphoma--2 (4%), and endometrium--1 (2%). Retreated patients received at least two courses of irradiation and one received three. The median interval between the first and second courses was 34 weeks (7.8 months). For the initial course of treatment, all patients were treated to the whole-brain with megavoltage X rays to a dose of 30-36 Gy (median 30 Gy) at 1.5 to 4.0 Gy/fraction (median 3.0 Gy/fraction). Retreatment also consisted of whole-brain irradiation (37/42 patients) to additional doses of 6-36 Gy (median 25 Gy) at 2.0 to 4.0 Gy/fraction (median 3.0 Gy/fraction). The total cumulative doses to the brain, therefore, varied from 38-75 Gy with a median of 60 Gy. Survival data were available for 42 of 44 patients retreated. All patients died with disease. The overall median survival following the initial course of irradiation was 40 weeks (9.2 months) with 10 patients (24%) living beyond 1 year. The median survival following retreatment, however, was only 8 weeks with one patient surviving greater than 1 year. Only 12 patients (27%) showed partial neurological improvement with re-irradiation and over one-half (55%) either failed to respond or deteriorated during or soon following retreatment. Brain necropsies were performed in 8 patients. Three of these had developed brain necrosis and two most likely died as a direct consequence. It is concluded that retreatment of brain metastases is seldom worthwhile. Survival is usually short and most importantly, the quality of survival frequently is not improved.

The role of gender and other factors in the prognosis of young patients with colorectal cancer.

Fifty patients from a socioeconomically disadvantaged population who were diagnosed when younger than 40 with colorectal cancer between 1968 and 1978 were analyzed. These patients had an increased survival compared with their older counterparts aged 40 years and older who were diagnosed during the same time. The young women had significantly better survival than the young men. Advanced stages, distribution of primary sites, and precancerous conditions were not major factors. The fact that the younger patients' cancers had a higher incidence of extracellular mucin production may have been counterbalanced by their receiving more extensive treatment. At the same time, cultural and social factors related to gender may have more to do with better survival than do factors evaluated in previous studies. In fact, because of the pervasive lack of male/female analysis, it is not known whether the survival difference due to gender found in this report is a universal tendency in young populations.

Palliation of inoperable head and heck cancer: combined intra-arterial infusion chemotherapy and irradiation.

Palliation of unresectable head and neck cancer remains a difficult problem. Because of excellent results reported by others with infusion of vinblastine, methotrexate, and 5-fluorouracil into the external carotid artery followed by irradiation before curative surgery, we applied this technic to 22 patients with advanced head and neck cancer. Fifteen patients from this group who had chemotherapy infusion followed by radiation therapy are compared with 21 patients who received radiation therapy alone. Both groups were similar in distribution of primary site, histology, and TNM stage. Of 15 patients, 14 (93%) had partial or complete tumor regression after both arterial chemotherapy infusion and irradiation, while 14 of 17 patients (82%) receiving primary irradiation had partial or complete response. Drug toxicity and complications related to infusion occurred in all patients. Most patients in both groups had short survivals (mean of 14.1 months in infusion chemotherapy and radiation vs 9.1 months in primary irradiation). One patient remains alive in the infusion group and two in the control group; however, all have recurrent disease. Results indicate a slight increase in survival time with the addition of infusionchemotherapy to irradiation in palliative treatment of head and heck cancer.

The impact of a special unit for terminal care

In October 1971 a special unit for terminal care was established in Sheffield, England (population 515,900) with a complement of 25 beds. During the preceding summer (May–August) it had been found that 279 people died in the city with an underlying diagnosis of cancer of pharynx, breast, bronchus, stomach, colon and rectum. Of these 44% died at home and 56% in hospital. In the summer of 1972 after the opening 278 people died of cancer of the same sites. The proportion who died at home was 41%, in hospital 49%, and in the special unit 9%. They did not differ significantly from the patients in the previous year in the distribution of primary sites, age, sex, marital status, or the availability and health of carers. Factors were identified in the medical and social circumstances of the patients which indicated a need for more care than could usually be provided at home. These consisted of the absence or poor health of a carer (usually the spouse), the level of help the carer had available, the period the patient was bedfast, the existence of severe symptoms and the necessity for special nursing procedures. A consideration of these indicated that although 96% of those patients who died in the special unit manifested one or more adverse factors (and 99% of those who died in hospital) there still remained 97 patients (35% of the total) who died at home who were also in this plight, indicating that the number of beds was probably still inadequate. There was increased activity by the community supporting services on behalf of the patients and their families in 1972, a possible spin-off from the opening of the unit.