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Background: Patient-reported outcomes have been used to assess treatment effectiveness and actively engage patients in their disease management. This study was designed to describe the patient-reported performance status (PS) and the provider-reported PS., Methods: Patients with metastatic genitourinary cancers were recruited from a single cancer center before the initiation of a new line of treatment. PS (Eastern Cooperative Oncology Group [ECOG]), quality of life (Functional Assessment of Chronic Illness Therapy-General), and distress (Patient-Reported Outcomes Measurement Information System Anxiety and Depression) were self-reported by patients. Clinical data (eg, age, sex, diagnosis, and physician-reported ECOG PS) were extracted from medical records. Multivariate analysis was used to determine the association between PS, quality of life, and psychological symptoms., Results: One hundred forty-five patients were enrolled (76.6% male, 70.3% White, 81.4% married, and 76.6% well educated). The median age was 67 years; 66.9% were diagnosed with renal cell carcinoma, 20.0% were diagnosed with urothelial carcinoma, and 13.1% were diagnosed with prostate cancer. Clinicians more frequently classified patients' ECOG PS as 0 in comparison with the patients themselves (92.4% vs 64.1%; P = .001). Higher clinician-reported ECOG PS was associated with poorer physical and functional well-being and higher rates of depression (P < .01), whereas higher patient-reported ECOG PS was associated with worse psychosocial outcomes (P < .01)., Conclusions: Discrepancies were noted between the patient- and provider-reported ECOG PS, with clinicians overestimating the ECOG PS in comparison with the patients themselves. This study's findings suggest that patients incorporate their social and emotional well-being into their PS score in addition to their physical well-being. This information is not immediately accessible to most clinicians from just a standard patient interview and likely accounts for the overestimation of the patients' ECOG PS by the clinicians., (© 2020 American Cancer Society.)

Background: Pediatric paired box 3:forkhead box protein O1 fusion-negative (PF-) rhabdomyosarcoma (RMS) represents a diverse spectrum of tumors with marked differences in histology, myogenic differentiation, and clinical behavior., Methods: This study sought to evaluate the clinical and mutational spectrum of 24 pediatric PF- human RMS tumors with high levels of myogenic differentiation. Tumors were sequenced with OncoPanel v.2, a panel consisting of the coding regions of 504 genes previously linked to human cancer., Results: Most of the tumors (19 of 24) arose at head/neck or genitourinary sites, and the overall survival rate was 100% with a median follow-up time of 4.6 years (range, 1.4-8.6 years). RAS pathway gene mutations were the most common mutations in PF-, highly differentiated RMS tumors. In addition, Hedgehog (Hh) and mechanistic target of rapamycin (mTOR) gene mutations with evidence for functional relevance (high-impact) were identified in subsets of tumors. The presence of Hh and mTOR pathway gene mutations was mutually exclusive and was associated with high-impact RAS pathway gene mutations in 3 of 4 Hh-mutated tumors and in 1 of 6 mTOR-mutated tumors., Conclusions: Interestingly, Hh and mTOR gene mutations were previously associated with rhabdomyomas, which are also known to preferentially arise at head/neck and genitourinary sites. Findings from this study further support the idea that PF-, highly differentiated RMS tumors and rhabdomyomas may represent a continuous spectrum of tumors. Cancer 2018;124:1973-81. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Background: Precancerous high-grade squamous intraepithelial lesion (HSIL), the current consensus terminology for anogenital squamous cell carcinoma in situ (SCCIS), often presents with distinctive histopathologic findings that may be a function of anatomic site or associated human papillomavirus infection., Methods: Fifty-six specimens of anogenital HSIL were compared with an equal number of specimens of SCCIS from non-anogenital sites in regard to the presence of parakeratosis, flag sign in the stratum corneum, compact stratum corneum, hypergranulosis, koilocytes, small blue cells, clonal populations of keratinocytes, pagetoid scatter of atypical keratinocytes, clear cell change, glassy red cytoplasm, pigmentation, nuclear/cytoplasmic(N/C) ratio >2/1, nuclear hyperchromasia, pleomorphic nuclei, mitotic figures, abnormal mitotic figures, dyskeratotic keratinocytes, involvement of skin appendages, acantholysis and amyloid deposition., Results: Hypergranulosis, koilocytes, small blue cells, pigmentation, nuclear hyperchromasia, dyskeratotic keratinocytes and amyloid deposition were more frequently noted in anogenital HSIL. Parakeratosis, clear cell change, pleomorphic nuclei, skin appendages involvement and acantholysis were strongly associated with non-anogenital location. There was no significant difference in the incidence of the remaining features., Conclusion: The strongest predicators of an anogenital location included hypergranulosis, koilocytes, small blue cells and nuclear hyperchromasia. Pigmentation and amyloid deposition were also strongly associated with an anogenital location., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The purpose of the present study was to examine the relationship between optimism and anxiety, depression and health-related quality of life (HRQOL). A further aim was to investigate the predictive value of optimism for anxiety, depression and HRQOL, quantified with and without controlling the corresponding base level., Methods: A total of 427 urogenital cancer patients were asked to complete the Life Orientation Test (LOT), the Hospital Anxiety and Depression Scale (HADS) and the health survey SF-8 during their stay in the hospital (T1), two weeks later (T2) and three months later., Results: Finally, 275 patients (64.4%) completed all questionnaires. Optimism at T1 was significantly associated with anxiety (r=-0.35), depression (r=-0.41) and HRQOL (physical: r=0.29; mental: r=0.27) and can predict outcome variables three months later. After controlling for the base levels of anxiety, depression and HRQOL, the predictive value of optimism remained significant but small. The incrementally variance explained by the LOT varied between 2.1% in anxiety and 8.2% in physical HRQOL., Conclusion: Especially patients with a low level of optimism and a high level of pessimism are at risk for higher levels of anxiety and depression in addition to lowered HRQOL., ((c) 2009 John Wiley & Sons, Ltd.)

Background: The aim of this study was to determine if extrapulmonary small cell carcinomas (EPSCC) should be managed using protocols similar to those for small cell lung cancer (SCLC)., Methods: Treatment strategies, survival, patterns of failure, and prognostic factors for patients with EPSCC were analyzed retrospectively at a large cancer center. SCLC was excluded by thoracic computed tomography (75%) or chest radiography (25%)., Results: Of 120 eligible patients, 70% had limited disease (LD). Treatment modalities included chemotherapy (n = 82; 68%), radiotherapy (RT) (n = 80; 67%), and surgery (n = 41, 34%). The median survival for patients with LD and extensive disease was 1.4 years and 0.7 years, respectively. Gynecologic (n = 31) and gastrointestinal (n = 28) were the most common primary tumor sites. Gynecologic and head and neck primary tumor sites had better 1-year survival than other sites (P = .019 and 0.005, respectively). Brain metastasis was the site of first distant failure in 4.1% of patients versus 35% for soft tissue metastases. The lifetime risk of brain metastasis was 13%. Definitive RT (P = .004), LD (P = .028), and prophylactic cranial irradiation (PCI) (P = .022) were found to be positive prognostic factors and weight loss (P < .001) was a negative prognostic factor on multivariate analysis., Conclusions: Patients with EPSCC usually experienced short survival, often with early distant metastasis. Although PCI was associated with improved overall survival, brain metastasis was less frequent than in patients with SCLC, and therefore the potential benefit of PCI was less than in patients with SCLC. Definitive chemoradiotherapy was associated with better outcomes and should be delivered whenever feasible.

Melanocytic lesions of the genital area are rare. They arise mainly in the vulva, although they can also occur less frequently in the perineum, mons pubis and male genitalia and represent 10-12% of pigmented lesions of White women. These pigmented lesions include melanocytic nevi, lentigines, melanocytic nevi with architectural disorder and atypia of melanocytes (dysplastic nevi) and melanomas with microscopic features similar to those seen elsewhere on the body. There is a small subset of benign nevi named atypical melanocytic nevi of the genital type (AMNGT) that occur in young women, with distinctive histologic features in some cases overlapping morphologically with those of melanoma. Thus, it is important to distinguish AMNGT from melanomas in terms of prognosis and treatment. We retrieved 58 cases of genital pigmented lesions diagnosed at our hospital from 1986 to 2008 to evaluate their clinicopathologic features with especial consideration to those cases with atypical features. Thirty-two cases (55%) were common nevi, 10 (17%) lentigines, 6 (10%) melanomas, 3 (5%) dysplastic nevi and 1 blue nevus. Six cases (10%) corresponded to AMNGT and were taken from women with a median age of 21 years. All cases showed symmetry, and the melanocytic proliferation was well demarcated at the lateral margins. The junctional component was very prominent and formed by round or fusiform nests with common retraction artifact and/or cellular dyshesion or as a single cell proliferation with mild (33%) to moderate (67%) cytologic atypia, focal pagetoid spread (17%) and a benign-appearing dermal component (83%) with maturation and dense eosinophilic fibrosis in the superficial dermis. Neither nuclear atypia of melanocytes in the superficial dermis nor dermal mitoses were observed. AMNGT were excised, and no recurrences were recorded in the follow up (median 10.5 years). Therefore, it seems that there is no evidence that AMNGT are precursors of dysplastic nevi or melanomas.

Background: Survival for rhabdomyosarcoma appears to be more favorable in children and adolescents compared with adults. To determine the significance of age at diagnosis as a prognostic indicator in rhabdomyosarcoma, we performed a retrospective analysis of a combined pediatric and adult rhabdomyosarcoma data base., Methods: Pertinent prognostic variables, including age, TNM stage, histopathologic subtype, anatomic site, resectability, radiation to the primary site, and dose intensity of chemotherapy, were compared in a Cox proportional hazards model with mortality as the outcome variable., Results: Age at diagnosis (P = 0.0001) and local tumor invasiveness (P < 0.0001), distant parenchymal metastases (P < 0.0001), regional lymph node involvement (P = 0.0027), and histopathologic subtype (P = 0.0446) contributed information to the proportional hazards model., Conclusions: Age at diagnosis is an independent predictor of outcome in patients with rhabdomyosarcoma along with tumor invasiveness, metastases, regional lymph node involvement, and histopathologic subtype.

Background: Extramammary Paget disease appears in anogenital, axillary, or other areas. In this study, the authors addressed the question of whether the histogenesis of 35 cases of Paget disease arising at different sites was the same., Methods: Specimens of 35 cases of extramammary Paget disease (16 genital; 9 invasive carcinomas of genital; 6 axillary; 1 periumbilical; and 3 perianal), 4 cases of mammary Paget disease, 4 cases of breast carcinomas, and 6 cases of anal carcinomas of perianal spread from primary rectal adenocarcinomas were retrieved and stained by the avidin-biotin-complex method, using various kinds of monoclonal antikeratin antibodies., Results: There was no significant difference in cytokeratin expression among these cases of extramammary Paget disease. Simple epithelial keratins were expressed in Paget cells in extramammary Paget disease, but no expression of differentiation-specific or noncornifying stratified squamous epithelial keratins was observed, regardless of the degree of invasion. Paget cells in extramammary Paget disease revealed a similar cytokeratin expression to that in secretory cells of normal apocrine or eccrine glands. In addition, there was no significant difference in cytokeratin expression in tumor cells among extramammary and mammary Paget disease, breast carcinomas, and anal carcinomas., Conclusions: Cases of Paget disease arising at different locations could not be distinguished from each other based on cytokeratin expression. In addition, antikeratin antibodies against simple epithelial keratins were demonstrated to be more useful for the identification of Paget cells in the paraffin sections than were conventional antibodies, such as an antibody against carcinoembryonic antigen (CEA).

The Radiation Therapy Oncology Group has conducted several randomized clinical trials to evaluate the efficacy of various radiation therapy schedules in palliating symptomatic brain and bone metastases. Among the patients entered in these studies, there were 225 patients with primary tumors of the genitourinary tract. Of these, 68 patients had cerebral metastases and 157 patients had osseous metastases. These patients were analyzed further as to the effectiveness of radiotherapy in palliation of their symptoms, and the results were compared to those for comparable metastases in patients with other primary sites. Relief of symptoms occurred in 54% of neurologic function (NF) Class III and 28% of NF Class II patients with cerebral metastases. This result compared favorably with those for the total group of patients consisting of patients with brain and bone metastases from various primary sites. Improvement was seen in 80% of patients with headaches and 88% of patients with convulsions. Motor loss improved in 62% of the patients. Of the patients with bone metastases, 81% with prostatic carcinoma and 59% with renal primaries had lessening of pain. Complete relief of pain at eight weeks occurred in 36% of the patients, compared to 24% in the total group. The median survival for patients with solitary bone metastases from a prostatic primary was 39 weeks, compared to 30 weeks for those with multiple metastatic sites.

Conditional five-year relative survival rates were calculated for patients diagnosed during 1950-1959 to examine long-term survival patterns for some of the more frequently occurring cancers. The data on the patients studied were collected as part of the national cancer institute's End Results Program. Breast cancer patients with localized disease were found to have only slightly increasing conditional rates for 20 years subsequent to diagnosis beginning at 85% at diagnosis and exceeding 90% at 20 years subsequent to diagnosis. Conditional five-year rates for patients with distant involvement approached the conditional rates for patients with regional involvement 15 years after diagnosis. Conditional rates by stage for patients with cancer of the cervix or cancer of the corpus increased initially and then became somewhat constant at a level related to stage of disease at diagnosis. For cancer of the colon, the conditional rates for female patients in each stage of disease category approached the same value 7-8 years subsequent to diagnosis. These observations may provide additional insight into the biological behavior of these cancers.

The catheter biopsy technique described by Melhoff and Osborne (1977) has been evaluated as a diagnostic aid in lower urinary tract disease in 21 animals. Of 16 animals in which the final diagnosis was known, the diagnosis suggested by the biopsy was accurate in 15. The equipment required for obtaining a biopsy is inexpensive and readily available and the method can be recommended for use in veterinary practice.

A series of 54 cases of embryonal rhabdomyosarcomas in adults were studied. The neoplasms were classified according to anatomic site, size, histologic pattern, age, and sex of the patients and modality of treatment. The major anatomic sites were the extremities (21 cases), genitourinary organs (13 cases) and the trunk (nine cases). The overall five-year survival rate was 21% but 79% of the patients were dead at an average time of 17 months after the primary diagnosis was made. On the other hand, 80% of the patients with Stage II disease (tumor size less than 5 cm) survived five years. In general, patients who were treated with surgery only or surgery and radiation or chemotherapy did much better than patients treated with chemotherapy and/or radiation therapy only. When the rate of recurrences, metastasis and time of death due to spread of neoplasm was compared in cases diagnosed between 1950-1969 and 1970-1978, patients in the last nine years had fewer recurrences, less metastases and better survival than those who had their neoplasm diagnosed and treated between 1950 and 1969.

Any patient who has a portion of a Y chromosome present should have gonadal extirpation to avoid the risk of gonadal neoplasia, whether benign or malignant. The following case history is presented to illustrate this risk and to lay aside the misconception that such patients are free from risk in the absence of an adnexal mass.

An unusually high association of other primary cancers (9.7%) was found during the analysis of 403 consecutive cases of carcinoma of the lung diagnosed at DGMC between 1960 and 1975. Incidence by stage included 17.3% for Stage I (75 cases) and 16.9% for Stage II (59 cases). Median survival by stage was not adversely affected by the associated malignancy. Incidence by histologic type was 15.6% for adenocarcinoma (132 cases), 7.7% for epidermoid (130 cases), 1.5% for oat (small cell) (67 cases), 12.5% for large cell (40 cases) and 11.8% for undifferentiated anaplastic type (34 cases). Of 31 cases of Stage I adenocarcinoma, 9 (29%) had second malignancies. Both adenocarcinoma and epidermoid carcinoma exhibited decreasing association of second malignances with increasing stage of lung cancer. The head and neck region was the location of the nonlung malignancy in 22 cases and the GU system in 11 cases. Two cases each of colon carcinoma and basal cell skin carcinoma were found and there was one case each of carcinoma of the pancreas, lymphoma and melanoma. The diagnosis of lung cancer was made first in only 3 instances. The appearance of solitary nodules in patients with known malignancy should receive strong consideration for vigorous diagnostic and therapeutic procedures. Future studies should consider carcinogenic stimuli that may be common etiologic factors in both malignancies.

Information on lesions that are metastatic to the bones of the feet is limited. Review of the literature revealed only 17 cases, nine of which were confirmed histologically. Our series involved the clinical records, roentgenograms, and pathologic specimens in eight cases of biopsy-proven metastatic involvement of the bones of the foot. In three additional cases, there was clinical and roentgenographic evidence of metastatic osseous foot lesion but biopsy was not done to provide histiolgic confirmation. Genitourinary malignancies tended to be associated with metastasis to the bones of the feet, the calcaneus being the commonest site of involvement. Although metastatic lesions of the foot are rare, foot pain may be suggestive of an occult carcinoma. Foot pain was the initial presenting complaint in five of our eight cases. The pathogenesis of these distal metastatic lesions remains obscure. Specific problems in management are associated with osseous metastases of the foot.

Tumor-bone interactions were experimentally studied using four transplantable human urogenital tumors in nude mice. The method consisted of subcutaneously (SC) inoculating tumor cells over the calvaria in nude mice after the periosteum has been disrupted. This resulted in a local tumor causing fragmentation of the bone. The degree of tumor-bone interaction also varied with the type of implanted tumors as shown in radiographic and histologic examinations. All tumors were associated with histologic patterns of classical bone remodeling, including bone destruction with osteoclast proliferation and reactive new bone formation. The evidence presented here suggests that the majority of tumor-bone interaction showed a combination of both features, bone destruction and new bone formation, and the mechanisms whereby tumors interact with bone may vary with the biological properties of the tumor. Our new system would be suitable for studying the biology of local interaction between bone and tumor cells and searching out a method to protect the bone from cancer cells.

Regional retroperitoneal lymphadenectomy usually is performed with radical nephrectomy for renal cell carcinoma and sometimes is performed with nephroureterectomy for upper tract urothelial tumors; however, no therapeutic benefit has been proven. Pelvic lymphadenectomy usually is performed with radical cystectomy for bladder cancer and may confer therapeutic benefit on patients having only minimal nodal involvement. A limited extraperitoneal pelvic lymphadenectomy, including only the nodes surrounding the obturator nerves, is performed in prostate cancer patients who are considered to be potential candidates for radical prostatectomy, but is of doubtful therapeutic benefit. The effectiveness of chemotherapy for germ-cell testicular tumors has diminished the utilization of routine surgical staging and also has decreased the scope of lymphadenectomy when performed. The substantial complications associated with traditional ilioinguinal lymphadenectomy for carcinoma of the penis and the unreliability of aspiration or excisional node biopsy have militated against routine surgical staging of patients having clinically negative nodes. This policy should be reconsidered in light of suboptimal treatment results and newer surgical techniques.

Computed tomography (CT) is currently the standard modality for staging of urologic cancer in most institutions. It is used for demonstrating nodal involvement, and for demonstrating invasion of the primary lesion into surrounding fat, muscle, or other tissues or organs. It is also useful for demonstrating hepatic metastases in renal and vesical carcinomas. The problem with computed tomography, however, is that it can only show whether the nodes are large or not; neither can it show the nodal architecture, nor can it detect metastases in normal-sized nodes. Intravesical sonography has been helpful for staging papillary bladder cancer. Transrectal sonography has been somewhat helpful for demonstrating seminal vesicle invasion in patients with prostatic carcinoma. Inferior vena cavography and renal venography can be helpful for demonstrating whether a renal, renal pelvic, or adrenal carcinoma has extended into either vein. Lymphography can show nodal architecture and metastases in normal-sized nodes, and can make possible needle biopsy of abnormal-appearing nodes even if they are normal sized. The examination cannot show very small or microscopic nodal metastases, and it can miss abnormal nodes totally if they have been completely replaced by metastases. It yields false positives when fatty or fibrous infiltration of the nodes has occurred. It is used primarily for staging patients with testis or prostatic carcinoma. Bone scans are essential for staging prostatic carcinoma. Magnetic resonance imaging (MRI) is helpful in some cases of renal cell carcinoma. Multiplanar imaging prevents overstaging. It is also accurate for showing whether the renal vein or inferior vena cava are involved. Enlarged lymph nodes are easily distinguished from vessels. For staging bladder carcinoma involving the fundus or base of the bladder, MRI is better than CT. Microscopic nodal metastases, such as are common in carcinoma of the prostate, currently are not detected by any imaging modality.

Clinico-pathologic reviews of series of children with rhabdomyosarcoma have yielded conflicting information regarding frequency of lymphatic spread of this disease. The 264 eligible entries in the Intergroup Rhabdomyosarcoma Study (from November 1972 to September 1975) have been categorized by a prospective staging system and pre-treatment characteristics and pathologic findings reviewed. Data accumulated thus far have revealed a higher than expected incidence of lymphatic metastases from extremity (17%) and genito-urinary sites (19%) with a somewhat lower incidence from the orbit (0%), the head and neck region (3%), and trunk (10%). These differences in regard to lymphatic metastases were found to have no relationship to age, sex, tumor size, or histologic type when these factors were simultaneously examined.

Significant advances in the therapy of genitourinary cancers have occurred, yet the challenge of metastatic disease in many of these tumors remains unsolved. The great success achieved in the treatment of testicular cancer has been in large part due to the development of effective systemic therapy. Effective treatment for metastatic transitional cell carcinoma is just beginning to be described. Advanced renal and prostatic carcinomas remain a major clinical problem with no effective curative therapy. Novel new approaches to systemic therapy developed on sound basic experimental principles are needed. Several potential approaches such as angiogenesis factor, interleukin II, lymphokine activated killer cells, and tumor necrosis factor are discussed.

The long term effects of initial therapy are a combined consequence of the effects of treatment on the cancer and on the host. Local tumor control, whatever its impact on the occurrence of metastasis, is an achievable and worthwhile goal of therapy and the methods for attaining it may have significantly different effects on quality of life. These considerations are grossly illustrated for renal cell, bladder and prostatic cancers.

The majority of findings in relation to warts have been passed on from one textbook to the other since the end of the last century. More recent studies have been carried out with the electron microscope. But information is lacking as to histology, histochemistry, examination with the phase-contrast microscope, with the interference microscope, microradiography and other new techniques. Warts are a proliferation of the epidermis caused by a virus, and we know that the culprit acts in the epidermis itself. Warts are acanthomas, and a transition to malignancy is possible in predisposed persons. It is most remarkable that in the malignant tumors of epidermodysplasia verruciformis, no virus could be found. As the demonstration of viruses with the electron microscope and other techniques cannot be made as a matter of routine, we have to search for a simpler method with the light microscope. With the application of more elaborate procedures, new information about epidermal proliferation will certainly be obtained.

One hundred and sixty-two patients with all types of soft tissue sarcoma, less than 21 years old and diagnosed at a single institution during the period 1958 through 1976, were studied. The major histologic subset comprised 115 patients with either embryonal rhabdomyosarcoma or undifferentiated sarcoma. In this group, responses of patients with stage I-II disease to local treatment alone indicated that at least half had no occult metastatic disease. Responses to irradiation alone in stage III disease indicated that only about a quarter of these patients had no occult disease. Sustained local control at the primary site by irradiation was observed in 68% of the patients given doses of 4,500 rad or greater compared with 22% at lower doses. The effectiveness of adjuvant chemotherapy was best seen in patients with stage III disease as a decrease in relapse rate and a lengthening of the time to first relapse. In these patients it appeared that occult metastatic disease could be eradicated in approximately half of the patients affected. In all the other varieties of soft tissue sarcoma in young people, recurrence at the primary site assumed relatively greater importance. This complication was markedly reduced in frequency when local postoperative irradiation was given in doses of 4,500 rad or greater. In this very heterogeneous group of malignancies, the value of adjuvant chemotherapy remained uncertain.

A few decades ago, there were few choices in the initial management of children with genitourinary tumors. Radical surgical removal was the only line of attack that promised any chance of survival. Improvement in the results of multimodal therapy in the last 15 years have radically altered the outlook for these children, hence the choice of therapy. As with other childhood cancers, the choice of therapy is based on risk-benefit evaluations of the roles of surgery, irradiation, and chemotherapy, since all three modalities have their associated morbidities. Current emphases are on preservation of function without compromising cure. The large cooperative clinical trials have emphasized this aspect of pediatric oncology. They have demonstrated, for example, that radiation therapy can be omitted from primary management of early stage Wilms' tumor patients who are given adequate adjuvant chemotherapy as can both radiation therapy and ablative surgery in certain cases of early stage rhabdomyosarcoma. Routine retroperitoneal node dissections have been shown to be of dubious diagnostic or therapeutic value in boys with testicular cancers. The need for bilateral oophorectomy in girls with dysgerminoma can similarly be questioned. Choices of initial therapy, therefore, are not static. They are becoming wider with each advance in multimodal therapy. Clinicians must keep abreast of the results of clinical trials so they can offer their patients the combination of treatments that will preserve function, and produce the smallest number of late complications without jeopardizing survival chances.