Seminoma of the testis: a 22-year experience with radiation therapy

An analysis is presented of 188 patients with a histological diagnosis of seminoma testis, treated by radical orchiectomy and radiation therapy between 1960 and 1981 at the Cross Cancer Institute. Using the Walter Reed Hospital staging classification, 149 (79%) patients were Stage I, 34 (18%) were Stage II, and 5 (3%) were Stage III. The 5-year survival for all stages was 90%, and for Stage I was 98%, Stage II, 71%, and Stage III, 0%. All were treated primarily with radiation therapy. Prophylactic mediastinal radiation was not employed for Stage I, and was employed in half of Stage II patients. Eleven patients with Stage I relapsed, five in the mediastinum and/or neck nodes. Eight of 11 were cured with further treatment. Stage II patients were subdivided according to the presence or absence of a palpable abdominal mass. Palpable disease (Stage IIB) carried a poorer prognosis. Three of 20 patients without a palpable mass (Stage IIA) died of disease; there was an 82% five-year survival rate. Eight of 14 with a palpable mass (Stage IIB) were cured by radiotherapy; there was a 54% five-year survival rate. All five Stage III patients died within 1 year of diagnosis. Stage I and IIA seminoma is curable by radiation alone. Prophylactic mediastinal radiation is not indicated in either Stage I or IIA disease. Long term toxicity from radiation is not seen. Optimal treatment for Stage IIB disease is undetermined and new treatment regimens should be explored. Stage III disease requires primary chemotherapy.     

Pregnancy and early-stage melanoma

BACKGROUND: Cutaneous melanomas are aggressive tumors with an unpredictable biologic behavior. It has been suggested that women who present with melanoma during pregnancy have a worse prognosis due to more aggressive behavior of the melanoma. The objective of the current study was to evaluate the long-term effect of pregnancy on disease progression in women with Stage I-II melanoma. METHODS: From 1965 to 2001, 46 pregnant women were treated for a Stage I-II melanoma at the University Medical Center Groningen. These patients were compared with an age-matched and gender-matched control group (nonpregnant) of 368 women with Stage I-II melanoma. The patients were staged according to the 2002 American Joint Committee on Cancer TNM classification system for melanoma. The 10-year disease-free survival (DFS) and 10-year overall survival (OS) rates were calculated using logistic regression analysis. RESULTS: The median age of patients in the pregnant group was 30 years (range, 18-46 years), and the median age of patients in the nonpregnant group was 36 years (range, 17-45 years). The median follow-up was 109 months (range, 1-356 months). Pregnant patients presented more often with thicker melanomas (median, 2.0 mm vs. 1.7 mm; not statistically significant). No differences with regard to tumor location, histologic subtype, tumor ulceration, or vascular invasion were detected between the pregnant group and the nonpregnant group. There was no statistical difference in the 10-year DFS and 10-year OS rates between the two groups. The 10-year DFS rates for patients in the pregnant and nonpregnant groups, respectively, were 88% versus 86% for patients with Stage I melanoma and 67% versus 73% for patients with Stage II melanoma. The 10-year OS rates for patients in the pregnant and nonpregnant groups, respectively, were 94% versus 90% for patients with Stage I melanoma and 82% versus 81% for patients with Stage II melanoma. CONCLUSIONS: Pregnancy does not appear to have an adverse, long-term effect on survival in patients with clinically localized melanoma. Further studies should address whether pregnant patients present with thicker lesions and/or whether they have decreased DFS compared with nonpregnant women. The prognosis for women with melanoma during pregnancy, as it relates to survival, still is dependent on tumor thickness and ulceration.     

Merkel cell carcinoma: experience of 14 cases and literature review

Merkel cell carcinoma is an aggressive skin cancer, with a significant incidence of locoregional lymphnode involvement, which requires timely diagnosis, adequate staging and aggressive therapy based essentially on surgical procedures. The aim of this study is to report our experience and to compare our results with literature findings, in order to discuss the role of the procedures adopted and their influence on prognosis. From July 1995 to April 2005, 14 patients were treated and followed-up for MCC in the National Cancer Institute of Naples. Tumor location was: buttocks (43%), extremities (36%) head (7%), unknown (14%). There were 7 Stage I, 5 Stage II and 2 Stage III patients. Surgical treatment consisted in wide excision (WE) in Stage I cases, WE and regional lymphadenectomy followed by radio- or chemo-therapy in Stage II and combined surgical and pre- and post-operative medical treatments in Stage III. Overall disease specific survival rate was 64% (median follow up 44 months). Recurrence occurred in 86% of Stage I and 20% of Stage II patients and involved, in 83.3% of Stage I patients, the lymph nodal draining basin. The treatment of recurrence implied surgery and radio or radiochemotherapy. Overall survival rate of recurrent patients was 57% (median follow-up 37.2 months). Due to the particular lymphotrophism of MCC, major care should be set on investigation and treatment of tumor lymph nodal draining basin. As long as the disease remains surgically manageable the prognosis for patients with MCC is favourable. The role of radio and chemotherapy is not yet assessed.     

Uncontrolled local recurrence after treatment of breast cancer with breast conservation

Three hundred fifty-six patients with early (Stage I and II) breast cancer and 55 with advanced (Stage III and IV) breast cancer were treated between 1979 and 1985 with a consistent policy of breast conservation irrespective of tumor site, size, or histologic features. Only three patients underwent primary mastectomy (Stage III), and the remainder were treated either by wide local excision and postoperative radiotherapy (357 cases) or by needle biopsy and primary irradiation (51 cases). A total of seven of 356 (2%) Stage I and II patients have developed uncontrolled local or nodal recurrence at a median follow-up of 5 years, and nine of 55 (16%) of Stage III and IV patients. Of the 62 Stage I and II patients who have died, seven (11%) have died with uncontrolled locoregional disease. Of the 22 Stage III and IV patients who have died, eight (36%) have died with uncontrolled locoregional disease. Although the majority of local recurrences within the conserved breast could be salvaged by secondary surgery (37/38 Stage I and II patients), the development of chest wall or nodal recurrence was usually associated with the appearance of distant metastases and a poor prognosis. Data on uncontrolled local recurrence should be given in all studies of breast cancer treatment, since it represents an important end-point of therapy and a difficult clinical problem.     

Seminoma of the testis: Results of treatment and patterns of failure after radiation therapy

Four hundred and forty-four patients with the histological diagnosis of pure seminoma were treated at The Princess Margaret Hospital between 1958 and 1976. Using the Walter Reed Hospital staging classification, 338 patients (76.1 %) were Stage I, 86 (19.4 %) were Stage II, and 20 (4.7%) were Stage III. The 5 year actuarial survival rate (5 yr S_A) for all stages was 87%, and for Stages I, II and III: 94%, 74% and 32% respectively. In Stage II the 5-year S_A was significantly worse when palpable abdominal disease was present (62%, vs 87% when it was absent, p < .02). Prophylactic mediastinal irradiation was not used for patients with Stage II disease. None of 40 Stage II patients without palpable abdominal disease recurred in the non-irradiated mediastinum. Ten of 46 Stage It patients with palpable abdominal disease recurred in the mediastinum; 7 of the 10 were cured with mediastinal irradiation at the time of relapse. Prophylactic mediastinal irradiation appears unnecessary in Stage II patients. The Stage III category includes a subgroup of patients who were curable with radiation therapy: $\text{5}\text{6}$ with supradiaphragmatic nodal disease without palpable abdominal or visceral disease were cured. Exploration of new treatment methods appears indicated for the salvage of patients recurring in sites other than the mediastinum or supraclavicular fossa and for patients presenting with visceral disease.     

Radiation therapy for the various subtypes of testicular seminoma

From 1964 to 1975 total of 53 consecutive patient with testicular seminoma were treated with irradiation post orchiectomy. The 3 year recurrence free survival, no evidence of disease (N.E.D.) was 97% for Stage I, and 93% for Stage II patients; 3 of 4 patients with Stage III disease were N.E.D. at 3 years. Elective irradiation to the mediastinum and supraclavicular area is indicated for Stage II but not for Stage 1. Spermatocytic and anaplastic subtypes have at least the same prognosis as classical seminoma and should be treated the same way. Two cases of seminoma with trophocarcinoma (embryonal carcinoma) are reported.     

Comparison of FIGO 1988 and 2009 staging systems for endometrial carcinoma

The objective of this study was to compare FIGO 1988 and 2009 endometrial carcinoma staging systems in terms of patient distribution and efficacy in predicting prognosis in patients treated with surgery and adjuvant radiotherapy (RT). Medical records of 351 patients treated between 1994 and 2009 were retrospectively analyzed. Adjuvant RT was in the form of vaginal cuff brachytherapy (BRT) in patients with uterine confined disease and risk factors, whereas high-risk patients received risk-adapted external pelvic RT. The median follow-up time was 55?months (range, 2.5-133?months). Five-year overall (OS) and disease-free survival (DFS) for the entire group was 83 and 88%, respectively. Stage migration was observed in 188 (54%) patients. Stage migration generally did not cause any significant effect in OS and DFS rates. However, 5-year OS and DFS for stage I patients with positive peritoneal cytology was significantly lower than the other patients with negative cytology in FIGO 2009 system. The survival curves overlapped for stage IA, IB and II in the new staging system. On the other hand, the division of stage IIIC as IIIC1 and IIIC2 significantly affected the prognosis. Patients with stage IIIC2 tumor had 40% OS and 48% DFS rates compared to 69 and 66% in stage IIIC1 patients (p?=?0.002). The major improvement of FIGO 2009 seems to be the subclassification of stage IIIC disease into IIIC1 and IIIC2. The positivity of peritoneal cytology per se seems to have an influence in prognosis in our cohort. To withdraw the positive cytology from staging may mislead the prognosis estimation in these patients and lead to undertreatment.     

Adverse effect of pregnancy on melanoma: a reappraisal.

The influence of pregnancy on the prognosis of cutaneous melanoma in women of childbearing age was examined in a retrospective review of 251 surgically treated cases. There was no statistical difference in survival at five years, free of disease, for Stage I melanoma between nulliparous, parous nonpregnant, and pregnant women. For Stage II melanoma, however, a significantly lower survival rate was observed for pregnant patients (29%) and parous women who had experienced activation of the lesion in a previous pregnancy (22%), as compared with that of nulliparous patients (55%) and other patients in the parous group (51%); p less than 0.05. This discrepancy in survival, together with the observed higher frequencies of Stage II cases, melanomas occurring on the trunk, and symptoms such as bleeding, ulceration, irritation, and elevation of the lesion, strongly suggest an adverse influence of pregnancy on women with Stage II melanoma.     

Hyperthermic adjuvant perfusion chemotherapy for Stage I malignant melanoma of the extremity with literature review

Thirty-nine patients with clinical Stage I malignant melanoma of the extremities were treated with hyperthermic perfusion chemotherapy using melphalan followed by excision or wide re-excision of the area and regional lymph node dissection. Four patients with positive lymph nodes, on histologic examination, were considered pathologic Stage II. Seventy-two patients with clinical Stage I extremity melanomas, who were treated by conventional surgical methods, served as concurrent controls, and were comparable in the distribution of their various pretreatment characteristics. The actuarial survivals for clinical Stage I perfusion patients calculated by the life-table method at 5, 10, and 15 years were 91%, 86%, and 77%, respectively, and disease-free survivals were 85%, 80%, and 80%, respectively. These figures were significantly better than controls. A Breslow depth of invasion of greater than 1.5 mm showed a significant difference in both clinical and pathologic Stage I disease as compared with the controls. Similarly, perfused patients aged less than or equal to 50 years survived significantly better than controls in both clinical and pathologic Stage I disease. The literature has been reviewed.     

Prognostic factors in head and neck melanoma. Effect of lesion location

Cutaneous malignant melanomas of the head and neck are prognostically engimatic. In addition to known prognostic determinants of stage and lesion microstage, lesion location also appears to have prognostic importance. The authors have reviewed a series of 83 microstaged head and neck melanoma patients in order to analyze the relative importance of these factors. There were 36 males and 47 females with a median age of 56 years. Eighty-one percent had pathologic Stage I disease, 7% were Stage II, and 12% were Stage III. The primary location was face in 32 patients, neck in 18, ear in 12, and scalp in 21 patients. The actuarial 5-year survival according to lesion thickness was 86% for melanoma less than 1.0 mm, 56% for 1 to 2 mm thick lesions, 47% for 2.1 to 4 mm thick lesions, and 25% for melanomas greater than 4.0 mm. The 5-year survival according to lesion location was 78% for facial and 58% for neck melanomas; for ear and scalp, the respective survivals were 33% and 37%. Median thickness was 2.0 mm for facial and 1.85 mm for neck lesions. It was 2.7 mm for ear and 2.0 mm for scalp lesions (differences not significant). There were no microstage factors that correlated with the adverse prognosis seen with scalp and ear melanomas. Multivariate analysis in the entire series (all clinical stages) showed the following to be significant: stage, thickness, and location of the primary melanoma (all less than 0.0002). In clinical Stage I melanoma, the significant prognostic factors were location (P = 0.035), thickness (P = 0.008), level (P = 0.024), and ulceration (P = 0.035). The prognosis of head and neck melanoma is uniquely influenced by location of the primary lesions in addition to stage, thickness, level, and ulceration, as observed with other cutaneous melanomas at other sites. Ear and scalp melanomas are high-risk lesions whose poor prognosis is not readily explained by any of the microstage factors reviewed.     

Hyperthermic isolated regional perfusion in the treatment of extremity melanoma in children and adolescents

From 1973 to 1982 six children and eight adolescents with extremity melanomas were treated by local excision and adjuvant hyperthermic isolated regional perfusion with Melphalan (L-phenylalanine mustard, manufactured by Burroughs Wellcome Company, Research Triangle Park, NC). The median Breslow thickness of the melanomas was 2.7 mm (range, 1 to 15 mm). According to the M.D. Anderson classification, nine patients were in Stage IA and five were in Stage IIIB. The median follow-up period was approximately 10 years. Distant metastases developed in three patients (21%) (one patient was in Stage IA [11%] and two patients were in Stage IIIB [40%]). In two cases the development of distant metastases was preceded by local recurrence (14%). The 5-year survival rate was 93%. The 10-year survival rate was 81%. The high survival rate, even for patients with unfavorably thick melanomas, seems to be attributable to isolated regional perfusion.     

Elective Neck Dissection for Management of Early-stage Oral Tongue Cancer

Background: The occult neck metastasis rate is very high with tongue cancers. The aim of this study was to assessthe current role of elective neck dissection (END) in management of early-stage oral tongue cancer with a focus onlymph node metastasis. In addition, effects of END on regional or systemic disease recurrence and survival wereinvestigated. Methods: This retrospective study included patients with stage I and II tongue cancer recruited fromour National Cancer Institute (NCI) over a time period of six years (2007-2013). The collected data were analyzed fordisease free survival (DFS) and recurrence rate. Results: A total of 144 patients presented to our NCI with oral tonguecancer but only 88 were staged clinically and radiologically as early stage (stage I, stage II). Some 53% were smokers.Most lesions were dealt with by surgery, either by wide local excision (22%) or hemiglossectomy (78%). Treatment ofneck lesions was either by neck dissection (85.2%) or “wait and see” (14.8%). The rates for local and nodal recurrencewere 7.9% and 20.4%, respectively. Analysis of associations between DFS and different factors revealed significancefor adoption of adjuvant therapy and the dissected lymph node status. Conclusion: Controversy still exists regardingneck management.     

Radiation therapy and conservation surgery for primary and recurrent carcinoma of the vulva: report of 40 patients and a review of the literature

Forty patients with histologically confirmed primary or recurrent vulvar carcinoma were treated with radiation therapy for loco-regional disease. Nineteen of the patients with primary tumors received postoperative radiotherapy (5000 cGy in 6 weeks). Fifteen of the 19 exhibited local tumor control. Five patients with Stage III or IV disease were managed with radiotherapy alone. Four had a complete response with two currently NED. Two patients who received preoperative radiotherapy with local excision are also currently free of disease. The 4-year NED survival for the study population is 100%, 28%, 50%, 0% and 10% for Stage I, II, III, IV and recurrent tumors respectively. The poor results obtained in Stage II tumors is likely due to selection criteria since four of seven patients developed distant metastases. Two of the 14 patients treated for recurrent disease remain NED after local excision of their tumors prior to irradiation. Even though the number of patients is small no dose response for subclinical disease could be found between 4500 and 7000 cGy. Treatment morbidity was acceptable with two patients developing severe long-term complications requiring surgical intervention.     

Vulvar carcinoma

: Controversies exist regarding the use of radiation therapy in the treatment of vulvar carcinoma. A retrospective review was performed to evaluate our institution's experience with surgery and radiation for this disease.

: The medical records of 47 patients treated for squamous cell carcinoma of the vulva at out institution (1974–1992) were reviewed for TNM stage (AJCC criteria), treatment modality, and associated 5-year local control and survival based on Kaplan-Meier analysis.

: Twenty-eight patients (60%) presented with Stage I and II disease and their 5-year survival was 69%. Stage III patients accounted for 12 (25%) of the patients and their 5-year survival was 73%. Seven patients presented with Stage IV disease and five died within 13 months of diagnosis after predominantly palliative therapy. The 40 patients with Stages I, II, and III disease were treated aggressively and were further evaluated for treatment-modality-associated survival and local control. Radiation therapy was used as primary treatment in nine patients, or whom seven were treated with radiation alone and two were treated postoperatively after wide excision. Surgery alone was performed in 31 patients consisting of either radical vulvectomy (20 patients) or wide excision (11 patients). When comparing outcomes of radical vulvectomy vs. radiation therapy, we noted that the 5-year actuarial survivals were comparable (74% for either modality), despite the presence of more favorable prognostic factors in the group treated with radical vulvectomy. Patients treated with wide excision alone had a trend for a poorer 5-year actuarial survival (51%) and local control (50%).

: Radical vulvectomy offers good locoregional control and survival. This retrospective review further supports the use of radiation therapy with conservative surgery as an alternative treatment option for patients with vulvar carcinoma treated with curative intent. In contrast, the use of wide excision alone should be performed with caution due to a higher locoregional failure rate. The role of appropriately prescribed radiation therapy should be further investigated in prospective clinical trials.     

Risk factors related to late metastases in 1,372 melanoma patients disease free more than 10 years

In many centers, Stage I–II melanoma patients are considered “cured” after 10 years of disease‐free survival and follow‐up visits are interrupted. However, melanoma may relapse also later. We retrospectively analyzed a cohort of 1,372 Stage I–II melanoma patients who were disease‐free 10 years after diagnosis. The aim of this study was to characterize patients who experienced a late recurrence and to compare them to those who remained disease‐free to identify possible predictive factors. Multivariate Cox proportional‐hazards regression analyses were carried out to evaluate the influence of different factors on the risk of recurrence. Seventy‐seven patients out of 1,372 (5.6%) relapsed, 52 in regional sites and 25 in distant ones. The majority of patients (31 out of 52) experienced late recurrence in regional lymph nodes. Brain and lung were the most common site of single distant recurrence (24% each). Patients with multiple distant metastases showed a brain and lung involvement in, respectively, 40 and 48% of cases. A Cox proportional‐hazards regression model analysis showed the independent role of age under 40 years, Breslow thickness >2 mm, and Clark Level IV/V in increasing the risk of Late Recurrence. These patients should be followed‐up for longer than 10 years. The pattern of recurrence suggests that melanoma cells can be dormant preferentially in lymph nodes, brain and lung. A particular attention should be reserved to these anatomic sites during the follow‐up after 10 years of disease‐free.     

Prognostic factors in patients undergoing curative irradiation for breast cancer

We have evaluated 147 patients who received primary curative irradiation for breast cancer to determine if there were any common factors that predisposed to failure. There were 10 local recurrences, for an overall local control rate of 93.2%, with a 2 to 16 year follow-up. Disease-free survivals were 85% in Stage I, 69% in Stage II, and 50% in Stage III. Age seemed to be a determinant, with a 31.6% local recurrence rate in women under 50 vs. a 3.1% rate of local recurrence in women age 50 or older when treated. We have also noted a correlation between the radiation dose and local recurrence, with a recurrence rate of 9.1% following a dose of 6000 rad or less, vs. a rate of 4.7% with a dose of 6400 rad or more. The size of the primary carcinoma and the status of the axillary lymph nodes, each considered individually, were not significant prognostic factors. There was no relationship between recurrence and the performance of an axillary dissection. There was evidence suggesting that the recurrence rate was lower when a wide local excision was performed, compared to a lesser procedure. Multiple foci of carcinoma and a high nuclear grade appear to have a poor prognosis. Five of the recurrences occurred early (under 2 years) and three of these were accompanied by fatal distant metastases. None of the five patients with late recurrences (37 to 116 months) developed metastatic disease, suggesting that late recurrences may have a better prognosis.     

Invasive carcinoma of the uterine cervix in women age 25 or less

The incidence of cervix cancer in young women appears to be increasing. However, the influence of young age on prognosis remains unknown. There is almost no information on the prognosis of very young women, age 25 years or less, with invasive cervical carcinoma. From April 1969 to June 1987, 40/2195 (1.8%) patients, age 25 years or less, with invasive carcinoma of the uterine cervix were diagnosed, staged, and treated at our institution. Median age was 24.7 years (range 20.7 to 25.9 years). Distribution by FIGO stage was: Stage IA 7 (18%), Stage IB 23 (58%), Stage II 4 (10%), Stage III 4 (10%), and Stage IVA 2 (4%). Thirty-four (85%) patients had squamous cell carcinoma and six (15%) had adenocarcinoma. Treatment consisted of radical hysterectomy for all Stage IA patients, radical hysterectomy with or without bilateral pelvic node dissection for the 12 early Stage IB patients, and radiation with or without surgery for the remaining 11 Stage IB patients and all Stage II-IVA patients. Median follow-up was 122 months (range 13.2-190.6 months). Five-year disease-free survival rates were: Stage IA 100%; Stage IB 54.8%; and Stage II-IVA 13.7%. Five-year disease-free survival for the Stage IB patients with squamous cell carcinoma age 25 years or less was 64.7%, compared with 83% for women of all ages with Stage IB squamous histology treated at our institution. Seven of 23 Stage IB patients suffered regional recurrence only, one a local recurrence only, one a distant recurrence only, and one a combined recurrence. Seventy-five percent of these patients presented with Stage I disease; however, one-third died from their disease. The major site of failure was in the pelvis only. This, coupled with the low risk of long-term serious complications, suggests that more aggressive pelvic therapy may result in improved disease-free survival.     

Patterns of local-regional recurrence and results in Stages I and II breast cancer treated by irradiation following limited surgery. An update

One hundred forty-six women with Stage I and Stage II breast cancer received radical radiotherapy after having excisional biopsy ( lumpectomy ) at Massachusetts General Hospital between 1956-1978. They were grouped according to age: those younger than 49 years and those older than 50 years. The 5-year survival rates were 93 and 73% for patients with Stage I and Stage II cancer, respectively; the corresponding 5-year relapse survival rates were 75 and 56%. The local recurrence rate was 8% in patients with Stage I disease and 17% in those with Stage II disease. Survival was not significantly affected by patients' age, by the presence or absence of blood vessel or lymphatic involvement, or by the addition of adjuvant chemotherapy. No major complications occurred. Modification in radiation dose and technique resulted in improved overall survival and local control. Limited surgery followed by radical radiation therapy offers a therapeutically effective, cosmetically acceptable alternative to radical surgery for early stage breast cancer.     

Adenocarcinoma of the uterine cervix

The prognosis of 589 patients with adenocarcinoma, 387 with mixed type of adenocarcinoma and squamous cell carcinoma of the uterine cervix from 18 hospitals in Japan were evaluated. Stage 0, I a patients with adenocarcinoma or mixed type had good survival. Stage I b, II, III patients had smaller five-year survival (p less than 0.01) than squamous cell carcinoma. Lymph nodes metastasis was related to poorer survival. Radiation therapy or chemotherapy was not sufficient for patients with stage I b, II, III, IV diseases.     

Regional lymph node metastases and the level of invasion of primary melanoma.

One hundred and nineteen patients with primary malignant melanoma had their primary lesion classified according to Clark's level of invasion by Clark and the Division of Surgical Pathology at UCLA. Thirty patients had superficial melanoma (Level II) and did not undergo regional lymph node dissection (RLND). All other patients (Levels III, IV, and V) underwent regional lymph node dissection. Thirty-two percent of patients with Level III melanoma, 67% of patients with Level IV melanoma, and 66% of patients with Level V melanoma had metastases to the regional lymph nodes. These studies suggest that the level of invasion, or the thickness of the primary melanoma, is helpful for predicting regional lymph node metastases.