The problem of neck relapse in early stage supraglottic cancer--results of different treatment modalities for the clinically negative neck

We reviewed the records of patients with Stage I and II epidermoid carcinoma of the supraglottic larynx treated at the Memorial Sloan-Kettering Cancer Center (MSKCC), New York, and at the Rotterdam Radio-Therapeutic Institute (RRTI), The Netherlands, between 1965 and 1979. At the MSKCC the treatment modality of choice for the primary tumor as well as for the neck had been surgery; of the 79 patients treated by surgery an elective neck dissection was performed on 31 patients. At the RRTI, however, the initial treatment for the primary tumor and the neck is radiation therapy. One-hundred and one patients were treated of whom 79% (80/101) had radiation therapy to the primary tumor as well as to both sides of the neck. This paper focuses on the problem of relapse in the neck, thus comparing patients treated in two large cancer centers by different treatment philosophies, that is elective neck dissection on one side of the neck versus elective radiation therapy to both sides of the neck. Twenty-nine percent of the patients from MSKCC (23/79) relapsed in the neck. The relapse rate was identical between the patients who did not have an elective radical neck dissection, and those who did. Among the patients who relapsed in the neck 65% (15/23) have died of the cancer, while among those who did not, none has died of supraglottic larynx cancer. Twenty-three percent (23/101) of the patients of the RRTI relapsed in the neck. Those who received radiation therapy to the primary tumor only relapsed regionally in 38% (8/21); treatment of both sides of the neck reduced the incidence of nodal recurrence to 19% (15/80). The majority of patients who relapsed in the neck eventually died of the cancer, that is 57% (13/23). Data from both institutions once again demonstrate the impact on survival of a relapse in the neck. Best strategies for decreasing the relapse rate in the neck are discussed; the conclusion was reached that, so far, elective radiation to both sides of the neck is the preferable treatment.     

Prognostic value of hemoglobin concentration in radiotherapy for cancer of supraglottic larynx

: The aim of this work is the estimation of correlations between hemoglobin concentration either before or after radiotherapy and local tumor control probablity for laryngeal cancer.

: Retrospective analysis of 847 cases of laryngeal supraglottic squamous cell carcinoma treated with radiation alone was perfomed using maximum likelihood estimations, and step-wise logistic regression. All patients were in good initial performance status (Karnofsky index >70). The minimum follow-up time was 3 years.

: Logistic regression showed that the hemoglobin concentration after radiotherapy is an important prognostic factor. There was a very strong correlation between hemoglobin concentration and tumor local control probability. Hemoglobin concentration at the beginning of radiotherapy does not correlate with treatment outcome, but any decrease of hemoglobin during therapy is a strong prognostic factor for treatment failure.

: Although regression models with many variables may be instable, the present results suggest that hemoglobin concentration after treatment is at least as important as overall treatment time. It was not possible to find out whether the low concentration of hemoglobin is an independent cause of low TCP or whether it reflects other mechanisms that may inlfuence both hemoglobin level and the TCP.     

Squamous cell carcinoma of the supraglottic larynx without clinically detectable lymph node metastases: problem of local relapse and influence of overall treatment time

From January 1965 until December 1979, 203 patients with squamous cell carcinoma of the supraglottic larynx were treated with curative intent. The mean follow-up time was 10 years. The policy was to try to aim for cure by radiation therapy (RT) only, reserving surgery (S) for radiation therapy failures. For 193 patients the treatment consisted of a first series of radiation therapy to a total dose of 40 Gy; if a good response to radiation therapy was obtained, the treatment was continued to a full course of 60-70 Gy (RT-I, n = 132). Patients with tumors considered to have responded poorly to the first series of radiation therapy but who refused surgery or were found medically unfit for operation, were also carried to a full dose of 60-70 Gy (RT-II, n = 33). Surgery was performed in 33 cases; 23 patients had a laryngectomy because of a poor response to radiation therapy and 10 were treated with surgery upfront because of severe respiratory distress. This paper focuses on the local control and survival in the defined treatment groups. In summary, with advancing T-stage a lower survival and higher local relapse rate was found; that is, a 5-year relapse-free survival (RFS) of 53% and corrected survival (CS) of 83% for T2 tumors vs 39% (RFS) and 52% (CS) for T4 tumors. Age more than 60 was associated with a 2.2 times higher risk of dying due to laryngeal cancer. A lower relapse-free survival (T3,4: 43% vs 61%) but a comparable corrected survival (T3,4: 64% vs 69%) for RT-I patients compared to the surgery treated patients was found, due to salvage of the radiation therapy failures. Although the relapse-free survival of RT-I and RT-II was similar (43% vs 38%), the corrected survival for the RT-II patients was worse (44% vs 69%). No influence of dose (Gy) per se on the local relapse rate was observed; however, a positive association between local relapse rate with overall treatment time was found. Death from intercurrent disease was almost twice as high as might have been expected for the normal Dutch population. More than half of the patients who died of intercurrent disease developed a second primary tumor.     

cN0声门上型喉癌的颈部复发相关因素分析

背景与目的：声门上型喉癌的隐性淋巴结转移率高,是此类喉癌诊治的重点之一。本研究旨在探讨声门上型喉癌的隐性淋巴结转移的相关因素、预后及治疗情况。方法：回顾分析1992-1999年我科收治的oNO声门上型喉癌104例。对其隐性淋巴结转移率、转移淋巴结的分布、影响隐性淋巴结转移的因素及颈部处理等进行研究。结果：本组cNO声门上型喉癌隐性淋巴结转移率为23．1％（24／104）,其中T2期23．9％（11／46）,T3期30．8％（8／26）,T4期18．5％（5／17）。隐性转移淋巴结主要位于病变侧Ⅱ、Ⅲ区（22／24）。出现隐性转移组预后差（log-rank=10．66．P=0．001）。切缘阳性影响隐性淋巴结转移率（χ^2=10．015,P=-0．002）。病理分化程度（χ^2=3．349,P=0．175）、T分期（χ^2=2．701,P=0．440）、原发灶处理方式（χ^2=1．093,P=0．296）等对隐性淋巴结转移率影响差异无统计学意义。颈部选择性清扫能降低cNO声门上型喉癌隐性淋巴结转移率（χ^2=4．070,P=0．044）。结论：cNO声门上型喉癌的隐性淋巴结转移主要位于病变侧Ⅱ、Ⅲ区;出现隐性淋巴结转移影响预后：切缘阳性影响隐性淋巴结转移率;对T1N0期喉癌颈部可观察,T2-4N0期喉癌行侧颈清扫（Ⅱ-Ⅳ区）是合理有效的。     

Lymphatic relapse in women with early breast cancer: a difficult management problem

The aim of this study was to review the ability to control symptoms of regional lymphatic relapse in women with early breast cancer. A retrospective study was made of 759 consecutive women presenting with stage 1 or 2 breast cancer treated by breast conserving surgery and radiotherapy between June 1984 and December 1994, 291 (38.3%) of whom were managed by a policy of observation on the lymphatic pathways. Patterns of lymphatic relapse, relapse management and morbidity caused by recurrent malignancy were reviewed from the case notes. The overall rate of relapse in the ipsilateral axilla and/or supraclavicular fossa was 76/759 (10%) at any time prior to death or last follow-up. 34 of 65 patients who relapsed in the axilla did so despite prior axillary surgery and/or radiotherapy. 41 of 76 patients with regional recurrence presented with symptoms, including lymphoedema, arm pain or sensory motor changes. These symptoms were poorly controlled by palliative surgery, radiotherapy or systemic therapy in 23 cases, including 12 who progressed to arm paralysis. Symptomatic control of patients with regional lymphatic relapse can be very difficult, even in women under regular surveillance in a multidisciplinary breast cancer clinic.     

The role of postradiotherapy neck dissection in supraglottic carcinoma

PURPOSE: To evaluate our policy of performing neck dissection based on regional response after definitive radiotherapy in patients with supraglottic carcinoma and to identify the prognostic factors in this group of patients. METHODS AND MATERIALS: Between 1970 and 1995, 121 patients with node-positive squamous cell carcinoma of the supraglottic larynx were treated with definitive radiotherapy. Sixty-nine percent of patients presented with 1997 AJCC Stage IV disease. The N-stage distribution was N1, 49; N2, 62; and N3, 10. The median size of the lymph nodes was 3 cm (range, 0.5-8 cm). Forty-five patients received once-a-day treatment with a median total dose of 65 Gy (range, 58.0-70.8 Gy) in 1.8-2.0 Gy per fraction over 48 days, and 76 patients received split-course accelerated hyperfractionation with a median total dose of 67.2 Gy (range, 63.2-73.6 Gy) in 1.6 Gy twice a day over 43 days. Patients whose lymph nodes were not clinically detectable at 4-6 weeks after the completion of radiotherapy (complete response) were followed without any neck dissection. Patients with persistent neck adenopathy (partial response) underwent neck dissection whenever possible. Mean follow-up of the living patients was 6.5 years. RESULTS: Regional response was related to the size of lymph nodes at presentation. Eighty-seven percent of patients with nodal size of 3 cm or less had a complete response, whereas 43% of patients with nodal size greater than 3 cm had a partial response. The rate of regional control at 3 years for all patients in the study was 66%. The 3-year ultimate regional control rate after salvage neck dissection was 75%. A relapse in both the primary and regional sites was the most common pattern of relapse, accounting for 39% of all the failures. Local failure was associated with subsequent regional relapse with a relative risk of 4.3. For patients with complete response in whom postradiotherapy neck dissection was withheld, the regional control rates were 75% and 86% for N1 and N2, respectively. The rate of isolated regional relapse in this group of patients was 7.5%. In multivariate analysis, significant favorable factors predictive for regional control were female gender, accelerated hyperfractionation, and complete response; whereas factors predictive for overall survival were Karnofsky Performance Scale score and regional response. The rate of Radiation Therapy Oncology Group (RTOG) Grade 2 or 3 neck fibrosis was 17% and 23% for patients with and without postradiotherapy neck dissection, respectively. CONCLUSION: Isolated regional relapse is not common in patients with supraglottic carcinoma when a complete response is achieved at 4-6 weeks after definitive radiotherapy and postradiotherapy neck dissection is not performed. Female gender, accelerated hyperfractionation, and complete response are favorable predictors of regional control.     

声门上型喉癌的外科治疗

目的总结声门上型喉癌外科治疗经验. 方法 390例声门上型喉癌全喉切除240例,部分喉切除150例.15例未行颈清扫,余同期颈清扫. 结果 Ⅰ、Ⅱ、Ⅲ、Ⅳ期全喉切除的5年生存率为83.3%,84.2%,53.1%,42.6%;部分喉切除为82.1%,83.6%,68.1%,55.6%.浸润型、结节型、浸润结节混合型的颈淋巴转移率分别为52.5%、8.43%、35.1%,平均37.4%.结论提倡部分喉切除.N1～3病例主张同期或分期双颈清,浸润型喉癌应全部行颈清扫.     

Patterns of breast relapse after local excision +/- radiotherapy for early stage breast cancer

One hundred patients with breast recurrence have been identified from patients at the Royal Marsden Hospital, treated by local excision +/- radiotherapy for early stage primary invasive breast cancer between 1961 and 1985. The mean follow-up was 58 months (range 1 month - 19 years). In 74/100 patients, breast recurrence occurred within the breast parenchyma, was not associated with systemic relapse and carried a relatively good prognosis with a median survival of 77 months from the time of breast relapse. In 67 patients with parenchymal relapse in whom the site of relapse could be reliably compared with that of the original tumour, 60 (90%) patients developed recurrent tumours at or close to the primary site. In 24/100 patients, breast recurrence occurred in the overlying skin and in only two of these patients (2% of total) did recurrence actually occur within the scar tissue. Skin relapse was associated with systemic relapse and carried a relatively poor prognosis with a median survival of 36 months from the time of recurrence. The pattern of breast relapse was similar in irradiated and unirradiated patients. Skin relapse appears to be a manifestation of metastatic disease while parenchymal relapse may represent regrowth of primary tumour. This pattern of breast relapse questions the requirement for radiotherapy to the whole breast after local excision for early stage breast cancer.     

Cancer of the supraglottic larynx treated by radiotherapy exclusively

Seventy-six cases of squamous cell carcinoma of the supraglottic larynx treated by radiotherapy exclusively and followed for at least 3 years are reported. High doses, close to the maximum tolerable, were used with the shrinking field technique with no attempt at prophylactic whole neck irradiation. T1 and T2 cases represented 40% of the whole group and 40% of the patients presented clinically positive neck disease. This latter group had a significantly lower cure rate (42.8%) than the N0 patients (88.3%). Disease control depended also on the T stage: all 30 T1 and T2 lesions, 18/22 (81.8%) of the T3, and 6/17 (35.3%) of the T4 lesions were controlled. Cord fixation and early cartilage destruction were not a major obstacle for tumor control. Base of tongue involvement and especially the T4 and N3 association were indications of poor prognosis. Adenopathies smaller than 3 cm were controlled in 14/16 cases while nodes greater than or equal to 3 cm were controlled in 5/11 cases. Failures in neck nodes outside the treatment field were encountered in 7% of the cases but as the sole element of failure they represented 5.6%. Absolute survival at 3 years was 69.7% for the whole series while loco-regional control was 74.6%. No patient was salvaged by surgery. Three loco-regional recurrences occurred 3 years after the treatment. Although no lethal complications were encountered severe late reactions were noted in about 20% of the patients with controlled primary lesion, requiring tracheostomy in 4 cases (7%). Treatment guidelines are suggested: T1, T2, & T3 lesions associated with adenopathy smaller than 3 cm should be treated by radiotherapy. Limited extra laryngeal extension especially to cartilage can still be controlled by irradiation. More advanced cases, especially the subcategory of T4 N3 patients, should have a multidisciplinary approach. After high doses of irradiation only limited surgery is permissible.     

Early distant relapse in early stage triple-negative breast cancer: usefulness of FDG-PET for diagnosis of distant metastases

Triple-negative breast cancer is extremely aggressive and more likely to metastasize than other subtypes of breast cancer. Better understanding of the distinct patterns of relapse and early detection will help identify patients who need aggressive treatment. Here we report a case of early stage triple-negative breast cancer with no lymph node metastasis at the time of breast-conserving surgery in a 46-year-old woman. She developed distant metastases immediately after completing adjuvant chemotherapy following surgery, which were detected by an [18F] 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scan. Although routine use of FDG-PET is not recommended for early stage breast cancer, FDG-PET might be useful for the early detection of distant metastasis among patients with triple-negative breast cancer.     

Site specific dependency of second primary cancer in early stage head and neck squamous cell carcinoma

BACKGROUND: A study was conducted to determine the site specificity of second primary cancer (SPC) following early (Stage I and II) squamous cell carcinoma of the head and neck (SCH) and its impact on prognosis. METHODS: Between 1956 and 1999, 1,639 early stage SCHs in 1,609 patients were treated by radiotherapy at the authors' institution. The risk of additional respiratory and upper digestive tract (RUDT) carcinoma and the treatment outcome were reviewed for each SCH site. Second primary RUDT carcinomas were the second most common cause of death (113 cases) after death from primary SCH carcinomas (350 cases). RESULTS: Among the 1,609 early stage SCH patients, 333 second primary cancers were documented in 258 patients, 235 (71%) of which were RUDT carcinomas. The risk of SPCs was 3.2% per year, and the risk of SPCs in the RUDT region was 2.3% per year. The risk of SPCs was almost two times higher in males (3.7% per year) than in females (2.2% per year). The highest risk of SPC was observed in the oro-hypopharynx index cancer group (8.5% per year), and the lowest risks were observed in the epipharynx group (0% per year) and the maxillary sinus group (1.4% per year). CONCLUSIONS: Different SPC risks according to the SCH site result in a different prognosis for each site of early stage SCH. Long-term follow-up care after the initial treatment for early SCH should be continued according to the site of the initial SCH.     

Radiation therapy for squamous cell carcinoma of the supraglottic larynx

Sixty-five patients with invasive squamous cell carcinoma of the supraglottic larynx received irradiation with curative intent between 1975 and 1984, with a 5-year actuarial survival of 48% and a local control rate of 70%. Five-year survivals for clinical Stages I, II, and III + IV were 60, 53, and 52%, respectively; local control rates were 88, 76, and 63%, respectively. These patients included one treated with preoperative irradiation, 35 treated with surgery followed by postoperative irradiation, and 29 treated with radiation therapy alone. In the surgery plus irradiation group, 5-year local control was 93% for clinical Stages I + II (14 patients), and 61% for clinical Stages III + IV (21 patients). Three patients had pathologic Stage II disease, with the remainder demonstrating a higher pathologic than clinical stage. Multiple positive nodes predisposed to local/regional recurrence, while no relationship could be established between recurrence and extracapsular nodal spread, positive margins, emergency tracheostomy, total versus less-than-total laryngectomy, radiation field size, radiation dose, or delay until radiation therapy, probably because of patient numbers. Six patients, five with positive nodes, developed distant metastases, and three developed second primary tumors outside the head and neck region. In the radiation therapy alone group, 5-year local control rates were 86, 59, and 53% for clinical Stages I (7 patients), II (11 patients), and III + IV (11 patients), respectively. However, three of four Stage II local/regional failures were surgically salvaged for periods greater than 30 months, for an ultimate Stage II local control of 89%. No relationship could be established between local control and radiation dose or field size, again probably because of small patient numbers. Three patients developed distant metastases, and eight developed second malignancies, one within the irradiated volume. Fifteen patients developed acute toxicity during irradiation, and there were eight chronic complications, five requiring surgery; toxicity was more common in the group treated with radiation alone. Radiation therapy alone with surgical salvage is an effective, function-preserving treatment for clinical Stages I and II carcinoma of the supraglottic larynx, and appears to yield local control and survival comparable with that of combined irradiation and surgery in more advanced disease.     

Leptomeningeal carcinomatosis from squamous cell carcinoma of the supraglottic larynx

Leptomeningeal carcinomatosis is an uncommon but devastating form of metastatic spread. To our knowledge, only 16 cases originating from a head and neck cancer have been reported. We describe the first case of a patient with leptomeningeal carcinomatosis arising from a laryngeal squamous cell carcinoma. Shortly after completing treatment for an advanced supraglottic laryngeal cancer, this 63‐year‐old man presented with lower limb neurological symptoms and signs. Radiological and cytological evidence of leptomeningeal carcinomatosis of the distal spinal canal was identified. He was treated with intrathecal methotrexate and palliative radiotherapy. Although his pain improved, his lower limb weakness worsened. He died 3 weeks after completing radiotherapy. Presumed mode of spread was via the haematogenous route. The natural history and management of leptomeningeal carcinomatosis are discussed. Clinicians should be aware of the uncommon possibility of leptomeningeal carcinomatosis in a patient presenting with an appropriate constellation of symptoms and signs, and a past history of cancer.