Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.

Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

Micronucleus formation kinetics in buccal mucosa cells of head and neck cancer patients undergoing radiotherapy.

In head and neck cancer, radiotherapy is one of the main treatment modalities besides surgery and chemotherapy either in a primary or an adjuvant setting. Radiation kills tumor cells by damaging the DNA within these cells. One of the methods to assess the degree of genomic damage is the micronucleus (MN) test. The effect of radiation therapy on the MN frequency in buccal mucosa cells has only been investigated in small studies looking at single time points or including a limited number of patients. In the present study, normal tissue buccal mucosa cells from 17 patients were analyzed for genomic damage at four different time points during radiation therapy. A clear increase was observed for every time point. Additionally, buccal mucosa cells of a cohort of 16 patients were analyzed after the end of the therapy and compared to samples from 25 patients sampled before the therapy. 10 healthy controls were included, of which 5 were sampled once, and 5 were sampled four times similar to the patients. Also, the influence of additional chemotherapy was investigated. No difference was observed between radiation-only patients and patients receiving additional chemotherapy. Age, gender, and tumor stage did not have an influence on the MN formation kinetics.

Salvage surgery after induction chemotherapy with paclitaxel/cisplatin and primary radiotherapy for advanced laryngeal and hypopharyngeal carcinomas.

Induction chemotherapy followed by primary radiotherapy in responders is considered an alternative to surgery for advanced cancer of the larynx and hypopharynx (LHC). Comparison of therapeutic approaches is challenging and must respect oncological and functional outcome as well as quality of life during and after treatment. One aspect of primary radiochemotherapy is the option of salvage surgery in case of residual tumor. The outcome after salvage surgery following new organ-preserving strategies has to be examined. All patients undergoing induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy from 01/96 to 07/05 were included. Salvage surgery was performed either for local recurrence or suspected persistent nodal disease. Complete tumor removal, perioperative morbidity, and overall survival were analyzed in a retrospective study. 28 out of 134 patients underwent salvage surgery after primary treatment with induction chemotherapy and radiotherapy for advanced LHC. 15 patients had laryngectomy (LE) with neck dissection (ND), while 1 patient had lasersurgical partial laryngeal resection with ND for local recurrences. Twelve patients had salvage ND for suspicion of persistent lymph node metastases. 73% of LE patients had major postoperative problems such as pharyngocutaneous fistulas. In 56% of the cases, tumor removal turned out to be microscopically incomplete. Eight out of 12 patients who underwent salvage ND because of suspicious lymph nodes (66%) were free of vital tumor. When metastatic disease was present in the neck (4/12), recurrences occurred in 75% during postoperative follow-up. Only 2 out of 20 patients undergoing surgery for histologically proven recurrence after radiochemotherapy (10%) are actually tumor-free and alive after a mean observation time of 43.9 months. Salvage surgery for local recurrence is associated with high morbidity and poor oncological and functional outcome. ND for suspicious persistent nodal disease after radiochemotherapy can be an over-treatment. In our patients, it was burdened with cervical recurrences and distant metastases in presence of histologically confirmed lymph node metastases. In the light of our results, unfavourable outcome after salvage surgery must be pointed out when initially informing patients about different therapeutic options for advanced LHC.

Approaches to preserve larynx function in locally advanced laryngeal and hypopharyngeal cancer.

Randomized controlled studies have shown that preservation of the larynx function in patients with advanced resectable laryngeal and hypopharyngeal cancer is possible without compromising survival compared to total laryngectomy (TL). Options for preserving the larynx include function-sparing surgery, radiotherapy alone, induction chemotherapy followed by radiotherapy of responders, and concomitant radiochemotherapy. The current data suggest that induction chemotherapy followed by radiotherapy of responders is an acceptable alternative to TL for patients desiring larynx preservation. Concomitant radiochemotherapy (platinum/5-FU) leads to superior local control and larynx preservation rates compared to induction chemotherapy followed by radiation. The optimal treatment sequence for newer cytotoxic agents is, however, unclear. Such cytotoxic agents and more effective fractionation regimens as well as more advanced surgical techniques are currently evaluated. Predictive tests to successfully stratify patients for the optimal treatment option and more effective systemic therapy are needed to improve therapeutic possibilities and survival.

[Carcinoma of the external ear canal and middle ear as interdisciplinary challenge for ear surgery and radiotherapy]. / Das Karzinom des äusseren Gehörgangs und des Mittelohres als interdisziplinäre Herausforderung für Otochirurgie und Strahlentherapie.

BACKGROUND: Carcinoma of the external auditory canal are tumours considered to have a poor prognosis. Improvement of the survival rate by surgical means alone is not possible. Individual therapy modalities as a result of an interdisciplinary approach between otosurgeon and radiotherapist are necessary. PATIENTS AND METHODS: A series of 30 patients (3 patients pretreated at other institutions) with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions was analysed with particular reference to tumour size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques. Clinical endpoints were freedom from local failure, overall survival, disease-free survival. The mean follow-up was 4.7 years (range: 0.1 to 18.8 years), median 3 years. RESULTS: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 51%. According to Pittsburgh classification the 5-year survival rate for early disease (T1- and T2-tumours) was 89%, for stage III 67% and for stage IV 39%. Most important prognostic factors were dural infiltration (all patients with dural invasion died within 2.2 years) and the infiltration of surgical margins (the 5-year survival rate of patients with complete tumour resection was 100%, but 54% in patients with tumour beyond surgical margins). 192-iridium HDR afterloading brachytherapy based on 3D CT-treatment planning is an effective tool in the management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSIONS: Surgical resection followed by radiotherapy adapted to the stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

Radiation techniques for head and neck tumors.

PURPOSE: A technique that combines some advantages of conforming techniques for advanced oro- and hypopharyngeal carcinomas is proposed. The aim is to increase the dose homogeneity in the target volume relative to lateral opposed fields. METHODS AND MATERIALS: This publication compares conforming radiation techniques based on standard equipment, standard linear accelerator setup and commercially available planning software with lateral opposed fields. More advanced conformal techniques reported in the literature are taken into account in a semi-quantitative manner. Our standard method uses an arc rotation, sparing the spinal cord. In contrast to earlier methods of this type, the resulting dose deficit in the vicinity of the spine is compensated by static lateral wedged fields. Dose distributions for 25 consecutive patients were planned. RESULTS: The conforming techniques were found to produce more homogeneous dose distributions than lateral opposed fields. In the planning target volume (PTV) (mean: 940 cm(3)) a standard deviation of dose of 4.6% was achieved. Ninety-five percent of the PTV were enclosed by the 90% isodose. The maximal spinal cord dose was limited to 45 Gy. The dose distributions of these techniques could compete with literature data on advanced techniques (the published dose-volume histogram (DVHs) of PTVs were evaluated). At the linear accelerator time for realization took 14 min on average. The planning time is 1-4 h (mean: less than 2 h). CONCLUSION: A rotational technique applicable with standard equipment is presented. Dose coverage of target volumes is improved, while the spinal cord is spared.

The influence of the radicality of resection and dose of postoperative radiation therapy on local control and survival in carcinomas of the upper aerodigestive tract.

PURPOSE: To evaluate dose concepts in postoperative irradiation of carcinomas of the upper aerodigestive tract according to the radicality of resection. PATIENTS AND METHODS: In a retrospective analysis, the charts of 257 patients with histologically-proven carcinoma of the upper aerodigestive tract (40 T1, 80 T2, 53 T3, 84 T4 tumors, with nodal involvement in 181 cases) were reviewed according to the radicality of resection and dose of irradiation administered. Sixty-four patients had tumor-free resection margins (> 3 mm), 66 patients had close resection margins (< 3 mm), and 101 patients had R1 resections, and 26 patients had R2 resections. A median dose of 56 Gy was applied to the primary tumor bed and the cervical lymphatics (2 Gy/fraction, 5 fractions/week). In cases of R1 or R2 resection, or of close margins (< 3 mm), the tumor bed or, respectively, tumor residuals were boosted with doses up to a median of 66 Gy. Locoregional tumor control and survival was investigated by uni- and multivariate analyses according to T-, N-stage, grade of resection, total dose of radiation, and presence or absence of extracapsular tumor spread and lymphangiosis carcinomatosa. RESULTS: An overall 3- and 5-year survival rate of 60% and 45%, respectively, was achieved. Rates for freedom from locoregional recurrence were 77% and 72% at 3 and 5 years, respectively. The survival rates according to the grade of resection at 5 years were 67% for patients resected with tumor-free margins, 59% for patients resected with close margins, 26% for patients with R1 resection, and 27% for patients with R2 resection. Within a median follow-up period of 4.7 years for living patients, a total of 67 recurrences (26%) were observed (in 9% of patients resected with tumor-free margins, in 27% with close margins, in 37% of R1 resected, and in 19% of R2 resected patients). Freedom from locoregional recurrence at 3 years was achieved in 100% of the patients resected with tumor-free margins, in 92% of patients resected with close surgical margins, in 87% of R1 and 69% of R2 resected patients. In multivariate Cox-regression analysis, the variables grade of resection (p = 0.00031) and total dose of irradiation (p = 0.0046) were found as factors influencing locoregional control. Variables influencing survival according to multivariate analysis are T-stage (p = 0.0057), N-stage (p = 0.024), grade of resection (p = 0.000015), total dose of irradiation (p < 0. 000000). Extracapsular tumor spread and lymphangiosis carcinomatosa are factors of borderline significance (p = 0.055, p = 0.066). CONCLUSION: In postoperative radiotherapy of head and neck carcinomas, doses adapted to the risk of locoregional recurrent disease should be applied. Patients with R1 and R2 resections should be treated with doses of more than 68 Gy (2 Gy/fraction, 5 fractions/week) (with close margins [< 3 mm] more than 66 Gy) to achieve an improvement in locoregional control and survival.

Systematics in lymphatic tumor spread of carcinomas of the upper aerodigestive tract--a clinical study based on embryologic data.

BACKGROUND: The aim of this study was to assess the incidence and pattern of cervical lymph node (LN) metastases in carcinomas of the upper aerodigestive tract in relation to primary tumor (PT) invasion of the equivalents of pharyngeal arches (PhA) and occipital and cervical somites (OCS) in adults. METHODS: The pretherapeutic computed tomography scans and clinical findings in 729 patients with histologically proven carcinoma of the upper aerodigestive tract (112 nasopharyngeal, 289 oropharyngeal, 252 laryngo-hypopharyngeal, and 76 oral cavity carcinomas, with LN involvement in 70% of the total) were analyzed in relation to PT invasion of equivalents of PhA and OCS. Tumors were recorded according to the infiltration of these equivalents. The metastatic involvement of the different cervical LN groups was analyzed and correlated to the pattern of PT invasion of equivalents of PhA and OCS by the chi-square test. RESULTS: The findings show that the pattern of cervical LN involvement depends on the location and extension of the PT and its invasion of equivalents of the PhA and OCS. Jugular LN metastases were found in tumors invading the equivalents of PhA 2-6. Submandibular LN metastases were evident in tumors invading tissues arising from the first PhA and the tongue. Retropharyngeal, spinal accessory and transversa colli LN metastases were found in tumors invading tissues arising from OCS. The frequency of LN metastases in the different LN chains decreased in the cranio-caudal direction. Each neck hemisphere showed separate lymphatic drainage. CONCLUSIONS: Analysis of PT extension in relation to PhA and OCS equivalents allows patterns of LN involvement to be predicted.

Carcinoma of the external auditory canal and middle ear.

PURPOSE: To evaluate therapeutic modalities used at our institutions regarding local control, disease-free survival and actuarial survival in carcinoma of the external auditory canal and middle ear, in an attempt to provide guidelines for therapy. METHODS AND MATERIALS: A series of 27 patients with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions were analyzed with particular reference to tumor size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques employed. Clinical endpoints were freedom from local failure, overall survival, and disease-free survival. The median follow-up was 2.7 years (range 0.1-17.9 years). RESULTS: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 61%. According to the Pittsburgh classification, the actuarial 5-year survival rate for early disease (T1 and T2 tumors) was 86%, for T3 tumors 50%, and T4 stages 41%. Patients with tumors limited to the external auditory canal had a 5-year survival rate of 100%, patients with tumor invasion of the temporal bone 63%, and patients with tumor infiltration beyond the temporal bone 38%. The rate of freedom from local recurrence was 50% at 5 years. Unresectability by dural and cerebral infiltration, and treatment factors such as complete resection or resection with tumor beyond surgical margins are of prognostic relevance. All patients with dural invasion died within 2.2 years. The actuarial 5-year survival rate of patients with complete tumor resection was 100%, but 66% in patients with tumor beyond surgical margins. 192Iridium high-dose-rate (HDR) afterloading brachytherapy based on three-dimensional computed tomography (3D CT)-treatment planning was an effective tool in management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSION: Surgical resection followed by radiotherapy adapted to stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

Tumor volume and local control in primary radiotherapy of nasopharyngeal carcinoma.

An investigation of the effect of tumor volume and total dose on local control following primary radiotherapy for nasopharyngeal carcinoma was carried out in order to estimate the radiation dose necessary to control a specific tumor volume. Between 1983 and 1996 a total of 104 patients underwent radiation therapy for nasopharyngeal carcinoma at the Department of Radiation Oncology of the University of Wuerzburg. Total doses of between 8 and 80 Gy (5 fractions per week) were administered. Complete CT-data on primary tumor size, total tumor dose (calculated by 3D- or quasi 3D-CT-based radiation planning computer) and on local control status in the follow-up period were available for 63 patients. Lymph node metastases were present in 38 of these patients and they were also entered into the study. Thus this study is based on a total of 101 tumor regions. A Poisson probability-based model was used for calculating the dose-response relationship. Assuming a correlation between tumor volume and the total dose necessary to obtain local control, the individual tumor volumes were rescaled to a 1 ml volume by introducing a volume-dependent modification factor for the applied dose, in order to eliminate the influence of different individual tumor volumes. All dose values given are based on a fractionation scheme of 2 Gy single dose, 5 fractions per week. Nineteen tumors and 11 lymph nodes were considered locally uncontrolled or recurrent. Without dose-volume modification, a weak dose-response correlation was found and a typical shallow dose-response curve was calculated with a 50% response dose (RD50) of 60.2 Gy and a normalized dose-response gradient (gamma50) of 3.2+/-0.62. After dose-volume modification and rescaling to a 1 ml tumor volume, a steep dose-response curve with an RD50 of 40.9 Gy and gamma50 of 8.2. was found. Tumor volume is a very important factor influencing local control in nasopharyngeal carcinoma. The rescaling procedure to a reference volume of 1 ml used in this study revealed a very steep dose-response relationship. This result suggests that the clinically observed smooth dose-response relationships may be explained by interindividual tumor volume heterogeneity. The additional dose necessary to control a tumor of the double volume is close to 5 Gy. With a total dose of 72 Gy (5x2 Gy/week), tumor volumes larger than 64 ml are unlikely to be controlled.

Cytotoxic and genotoxic effects of paclitaxel (Taxol) and radiation in a squamous cell carcinoma cell line of the larynx.

Paclitaxel (Taxol) is an antimicrotubular agent which blocks the cells in the G2/M phase of the cell cycle. Because of this mechanism it is presumed that this drug could function as a radiation sensitizer. The cytotoxic and genotoxic effects of paclitaxel and a combination of paclitaxel and radiation were studied in the human laryngeal carcinoma cell line HLac 79. The growth of the cells was significantly reduced at concentrations of paclitaxel as low as 10 nM. Flow cytometry data showed a G2/M block after exposure to paclitaxel. Radiation at 12 and 24 h after drug treatment exerted an additive but no radiation sensitizing effect. As genotoxic effect paclitaxel induced multinucleated cells, possibly in a synergistic manner, at low concentrations (10 nM) and radiation doses up to 3 Gy.

[3D-Ct-planned interstitial HDR brachytherapy + percutaneous irradiation and chemotherapy in inoperable pancreatic carcinoma. Methods and clinical outcome]. / 3D-CT-geplante interstitielle HDR-Brachytherapie + perkutane Bestrahlung und Chemotherapie bei inoperablen Pankreaskarzinomen. Methodik und klinische Ergebnisse.

PURPOSE: Clinical experiences in interstitial 192-iridium HDR brachytherapy for the treatment of unresectable pancreatic carcinoma are presented. Brachytherapy has been used as boost irradiation in a multimodality treatment concept together with external radiotherapy and simultaneous chemotherapy. Practicability during clinical routine, tolerability and toxicity of treatment are investigated. PATIENTS AND METHODS: Nineteen patients (9 female, 10 male, median age 67 years) with unresectable carcinoma of the pancreas have been treated with interstitial brachytherapy. Distribution according to UICC stages showed 4, 10 and 5 patients in stage II to IV respectively. In all cases afterloading technique with 192-iridium in HDR-modus was used. A total dose of 10 to 34 Gy to the reference isodose was delivered (single dose 1.88 to 5 Gy, median 2.5 Gy). Brachytherapy was followed by external radiotherapy, delivering an additional dose of 40 to 58 Gy. Nine patients received simultaneous chemotherapy (5-fluorouracil, leucovorin). Treatment planning was performed based on CT scans, allowing spatial correlation of isodose curves to the patient's anatomy. RESULTS: Median survival time was 6 months. A trend of lower survival rates with advanced stage of disease (median survival stage IV 4 months, stage II and III 6.5 months) was seen. Local control rate was 70%. Brachytherapy treatment was well tolerated, severe acute side effects were not observed. One patient developed pancreatic fistulae 4 months and 1 patient a gastric ulcer 7 months after treatment. Pain release was achieved in all patients. CONCLUSIONS: 192-iridium HDR-brachytherapy is an effective tool in the treatment of unresectable pancreatic carcinoma with a high rate of local control and a low rate of side effects and is comparable IORT or seed implantation.

[Systematic analysis of cervical lymph node metastasis of larynx and hypopharynx carcinomas--a clinical computerized tomography study with special reference to extension of the primary tumor]. / Systematik der zervikalen Lymphknotenmetastasierung von Larynx- und Hypopharynxkarzinomen--Eine klinisch-computertomographische Studie unter besonderer Berücksichtigung der Ausdehnung des Primärtumors.

PURPOSE: To assess the incidence and patterns of cervical lymph node metastases in laryngeal and hypopharyngeal carcinomas according to the location, extension, and relation of the primary tumor to the parapharyngeal compartments and tissues arising from different embryological structures as branchial arches and somites. PATIENTS AND METHODS: The findings of clinical and CT examinations of 230 patients with histological evidence of laryngeal and hypopharyngeal carcinoma (44 T1-, 33 T2-, 41 T3-, 112 T4-carcinomas with lymph node involvement in 116 cases) were evaluated retrospectively. Local tumor spread and relation of the primary to the parapharyngeal compartments and to tissues arising from different embryological structures such as branchial arches and somites were analysed and related to cervical lymph node involvement. RESULTS: The pattern of cervical lymph node involvement depends upon location and extension of the primary tumor in the adjacent tissues of the larynx and hypopharynx. The density of the lymphatic vessels in these areas determines the likelihood of lymph node involvement. The frequency of NO cases in carcinomas strictly located in the vocal cord (n = 31) was 100%; in the glottic-supraglottic, supraglottic, and transglottic cancer (n = 106) 85%; in larynx-hypopharynx carcinomas (n = 54) 26%; in hypopharynx carcinomas (n = 12) 17%; and in larynx-hypo-oropharynx carcinomas (n = 46) 9%. Tumors in tissues arising from branchial arches 4, 5, and 6 are glottic-supraglottic, transglottic laryngeal, and laryngeal-hypopharyngeal carcinomas. Metastases of these tumors were frequently found in the jugular lymph node chains, particularly if the developed tissue of the "primitive glottis" was invaded by the primary. Upper jugular nodes ipsilateral to a supraglottic or hypopharyngeal primary were usually involved. The frequency of metastases in the jugular lymph node chains decreased in craniocaudal direction. If the tumor invaded the posterior wall of the hypopharynx or tissues.

[Analysis of cervical lymph node metastasis of oropharyngeal carcinoma in relation to extent of the primary tumor]. / Analyse der zervikalen Lymphknotenmetastasierung von Oropharynxkarzinomen in Abhängigkeit von der Ausdehnung des Primärtumors.

PURPOSE: To assess the incidence and patterns of cervical lymph node involvement according to the location and the relation of the primary tumour to the parapharyngeal fasciae, compartments and tissues arising from different branchial arches. PATIENTS AND METHODS: The findings of clinical and CT examinations of 143 patients with histological evidence of oropharyngeal carcinoma were evaluated retrospectively. Local tumour spread, relation of the primary to the parapharyngeal fasciae, compartments and to the borders of tissues arising from different branchial arches were analysed and related to cervical lymph node involvement. RESULTS: Lymph drainage of the oropharynx and neighbouring neck regions is determined by the embryological development of the branchial arches and somites. Oropharyngeal carcinomas are tumours arising from tissues of the 2nd and 3rd branchial arches. The lymph of these tissues is collected by the vessels of the jugular neck node chains. If tumour invades tissues arising from the 1st branchial arch (structures of the oral cavity and floor of the mouth) tumour spreads into the ipsilateral lymphatic vessels arising from the 1st branchial arch and the submaxillary lymph nodes. If tumor invades tissues arising from occipital and cervical somites (posterior wall of the nasopharynx, retropharyngeal compartment and recessus submuscularis) metastases in the retropharyngeal and spinal-accessorial lymph nodes may appear. Regarding the tumour invasion of the subdistricts of the oropharynx totally different tumours were found. Tumour invasion of neighbouring structures was documented for the nasopharynx in 15%, for oral cavity and the floor of the mouth in 34%, the larynx in 24% and the hypopharynx in 22% of the cases. From these different patterns of local tumour spread different patterns of lymph node involvement resulted. Nodal involvement was found in 71%. In all these cases metastases in the ipsilateral upper jugular lymph nodes were present. The frequency of metastases in the jugular lymph node chains decreased in cranio-caudad direction (upper jugular group 100%, middle 18%, lower jugular group 5%). The frequency of bilateral jugular lymph node involvement (25%) increased in the some measure as the tumour approached the midline or crossed it. CONCLUSIONS: Knowledge of regular patterns of spread of oropharyngeal carcinoma is important for treatment procedures, especially for 3-dimensional radiotherapy.

[Systematic analysis of local growth behavior and cervical lymph node metastasis of nasopharyngeal carcinoma--a clinical and computerized tomography examination]. / Systematische Analyse des lokalen Wachstumsverhaltens und der zervikalen Lymphknotenmetastasierung von Nasopharynxkarzinomen--eine klinisch- computertomographische Untersuchung.

BACKGROUND: Assessment of the incidence and patterns of cervical lymph node involvement according to the location, extension, and histological subtype of nasopharyngeal carcinoma. PATIENTS AND METHODS: The findings of the clinical and CT examinations of 80 patients with histological evidence of nasopharyngeal carcinoma (9T1-, 20 T2-, 17 T3-, 34 T4-carcinomas, lymph node involvement in 59 cases) were evaluated retrospectively. The histological subtype, local tumor spread, relation of the primary to the parapharyngeal fascias, compartments, and skull base structures were analysed and related to the cervical lymph node involvement. RESULTS: Two main types of nasopharyngeal carcinomas with different patterns of cervical lymph node involvement were identified: the posterior wall type, which spreads into the retropharyngeal and spinal accessorial neck node chains and the ventral type, which is located which is located at the roof, anterior, and lateral walls of the nasopharynx and spreads into the jugular neck node chains, preferring the neck side in which the main part of the primary is located. The border of lymph drainage via retropharyngeal-spinal accessorial or via jugular neck node chains is localised ventral of the origin of the m. capitus longus at the skull base. If the primary involves the prestyloidal compartment, the tumor may spread into the ipsilateral submaxillary lymph nodes. Combinations of the different types are frequently found with the neck node spread following the described directions. CONCLUSIONS: Knowledge of the regular patterns of spread of nasopharyngeal carcinoma is important for treatment procedures, especially for planning 3-dimensional radiotherapy.

Combined isodose curves of high-dose rate interstitial brachytherapy with external-beam radiation therapy in pancreatic carcinoma.

From September 1989 until March 1992 nine patients with unresectable, though localized carcinoma of the pancreas were treated by a multimodality therapy consisting of palliative surgery, interstitial conformal brachytherapy in high-dose rate mode (HDRBT) with iridium-192 up to 30 Gy and external-beam radiation therapy (EBRT) of about 52 Gy. Four patients simultaneously received two cycles of chemotherapy consisting of 5-FU and Leucovorin. Since high radiation doses are applied which are not tolerated in adjacent healthy tissues, doses to tumor and critical areas need to be known precisely and are to be adjusted before treatment. A three-dimensional imaging system is required. A self developed method combines the data of simulation radiographs and those of CT scans. The prescribed minimum target absorbed dose in HDRBT is adjusted to the target volume sparing organs at risk. The specialized quality assurance is adapted to this method. Differences between measured and calculated doses do not exceed 5%. The addition of isodoses of HDRBT and EBRT on CT scans is demonstrated. Due to patients' selection the treatment concept did not reveal any positive effects on survival. However, excellent palliative results were obtained without severe side-effects.