[Translated article] Role of radiotherapy in the management of spine metastases.

Spine metastases are a common cause of pain in the oncologic patient which can generate functional limitation, in addition to complications derived from spinal cord compression, radicular compression and fractures. A complex approach to these metastases is required due to the risk of permanent sequelae. With the increase in survival rates due to new emerging treatments, the possibilities of presenting vertebral metastases are increasing, therefore, the management of these lesions should be aimed at pain relief and maintenance of ambulation. Radiotherapy has a fundamental role in the management of these lesions, and technological advances in recent years have made it possible to improve the quality and intentionality of the treatments, going from having a palliative intent to proposing treatments that improve local control. In this article, we describe how the stereotactic body radiotherapy (SBRT) technique, in selected patients, can improve local control and its value in oligometastatic patients and after surgery.

Role of radiotherapy in the management of spine metastases. / Papel de la radioterapia en el manejo de las metástasis vertebrales: últimas novedades.

Spine metastases are a common cause of pain in the oncologic patient which can generate functional limitation, in addition to complications derived from spinal cord compression, radicular compression and fractures. A complex approach to these metastases is required due to the risk of permanent sequelae. With the increase in survival rates due to new emerging treatments, the possibilities of presenting vertebral metastases are increasing, therefore, the management of these lesions should be aimed at pain relief and maintenance of ambulation. Radiotherapy has a fundamental role in the management of these lesions, and technological advances in recent years have made it possible to improve the quality and intentionality of the treatments, going from having a palliative intent to proposing treatments that improve local control. In this article we describe how the stereotactic body radiotherapy (SBRT) technique, in selected patients, can improve local control and its value in oligometastatic patients and after surgery.

Outcome and toxicity of intensity-modulated radiotherapy with simultaneous integrated boost in patients with pharyngo-laryngeal cancer.

PURPOSE: The present work aims at evaluating intensity-modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) in squamous cell carcinomas (SCC) of the larynx and hypopharynx. METHODS/PATIENTS: We performed a single institutional retrospective analysis on 116 pharyngo (29%)-laryngeal (71%) SCC patients (93% male) treated with IMRT-SIB to 66-69.96 Gy in 33 fractions between 2008 and 2016. Those who underwent surgery (54%) received adjuvant radiation of 66 Gy at 2 Gy/fraction to the surgical bed. 16 patients (14%) were treated for a local recurrence after prior surgery. High-risk lymph node regions received 59.4 Gy at 1.8 Gy/fraction and low risk regions 54.12 Gy at 1.64 Gy/fraction. The median age was 60 years and 95% of patients had an ECOG performance status 0-2. Most had advanced stage disease (III 22%, IV 74%). Chemotherapy was delivered in 74% of cases. RESULTS: Median follow-up was 32 months. Two and three-year overall survival for all patients was 87% and 82%, respectively. There were 28 (24%) locoregional recurrences and 19 (16%) distant failures. Grade 3 mucositis, dermatitis, and xerostomy were observed in 12%, 10%, and 3%, respectively. A longer IMRT-SIB overall treatment time was associated with a higher risk of mortality (HR 1.09, CI 1.01-1.17, P = 0.02). Postoperative IMRT-SIB associated with a significantly lower risk of any recurrence (HR 0.34, CI 0.18-0.64, P = 0.001) and higher local control (HR 0.06, CI 0.01-0.24, P < 0.01). Additionally, it associated with a lower risk of mucositis (P = 0.029) compared with definitive radio (chemo) therapy. CONCLUSIONS: IMRT-SIB is a safe and feasible radiation treatment technique for pharyngo-laryngeal SCC patients with a tolerable acute toxicity profile.

Outcome and toxicity of intensity modulated radiotherapy with simultaneous integrated boost in locally advanced non-small cell lung cancer patients.

PURPOSE: The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction. RESULTS: The median follow-up was 16 months (range, 1-70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022). CONCLUSION: This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy.

Effectiveness and toxicity of helical tomotherapy for patients with locally recurrent nasopharyngeal carcinoma.

PURPOSE: We assessed therapeutic outcomes of reirradiation with helical tomotherapy (HT) for locoregional recurrent nasopharyngeal carcinoma (LRNPC) patients. METHODS AND MATERIALS: Treatment outcomes were evaluated retrospectively in 17 consecutive LRNPC patients receiving HT between 2006 and 2012. Median age was 57 years and most patients (n = 13) were male. Simultaneous systemic therapy was applied in 5 patients. Initial treatment covered the gross tumor volume with a median dose of 70 Gy (60-81.6 Gy). Reirradiation was confined to the local relapse region with a median dose of 63 Gy (50-70.2 Gy), resulting in a median cumulative dose of 134 Gy (122-148.2 Gy). The median time interval between initial and subsequent treatment was 42 months (11-126). RESULTS: The median follow-up for the entire cohort was 23 and 35 months for survivors. Three patients (18 %) developed both local and distant recurrences and only one patient (6 %) suffered from isolated local recurrence. Two-year actuarial DFS and LC rates were 74 and 82 %, respectively. Two-year OS rate was 79 %. Acute and late grade 2 toxicities were observed in 8 patients (47 %). No patient experienced late grade ≥3 toxicity. Late toxicity included fibrosis of skin, hypoacusia, dysphagia, and xerostomia. Patients with higher Karnofsky performance status scores associated with a lower risk of mortality (HR 0.85, p = 0.015). CONCLUSION: Reirradiation with HT in patients with LRNPC is feasible and yields encouraging results in terms of local control and overall survival with acceptable toxicity.

Intraoperative EBRT and resection for renal cell carcinoma : twenty-year outcomes.

PURPOSE: We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. PATIENTS AND METHODS: From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. RESULTS: Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. CONCLUSION: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation.

Analysis of fiducial markers used for on-line verification in the external-beam radiotherapy of patients with cranial tumours.

PURPOSE: Evaluate the fiducial marker-based position verification in the external-beam radiotherapy of patients with cranial tumour. METHODS: Thirteen patients with intracranial tumours were treated with external- beam radiotherapy using 3 gold markers implanted in the skull. Before each fraction the patient was positioned on the treatment table and 2 orthogonal portal images were performed to localise the 3 gold seeds and the target position was calculated using a commercialised computer program (ISOLOC software, MEDTEC). This program provides the couch movements required to move the target to the isocentre. RESULTS: When the set-up error was corrected using the coordinates of the 3 markers, the final movements were less than 2 mm in all cases: lateral, mean v., 1.21 mm; longitudinal, 1.23 mm; and anteroposterior, 1.18 mm. No serious complications related to the gold marker insertion were noted. CONCLUSION: The use of 3 implanted fiducial seeds is an optimal technique for precise set-up in patients with brain tumours treated with external radiotherapy. This commercial system is highly suitable for fractionated stereotactic irradiation.

Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study.

The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m(2) plus doxorubicin 80 mg/m(2) alternating every 14 days with paclitaxel 200-350 mg/m(2) plus cisplatin 120 mg/m(2). Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m(2) plus etoposide 600 mg/m(2) alternating with paclitaxel 200-350 mg/m(2) plus ifosfamide 8 g/m(2). Peripheral blood stem cells were infused after every course except the first, with a median CD34(+) dose of 2.1 x 10(6)/kg per cycle. Positive selection of CD34(+) cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support.

[Effect of PSA nadir and the time to nadir in the disease-free period in localized prostatic carcinoma treated with radical radiation]. / Influencia del nadir de PSA y el tiempo a nadir en el periodo libre de enfermedad (PLE) del carcinoma prostático localizado tratado con irradiación radical.

OBJECTIVE: To evaluate the prognostic significance of PSA nadir (nPSA) and the time to nadir in disease free of recurrence (DFR) in localized carcinoma of prostate treated with radical radiotherapy (RTR). MATERIAL AND METHODS: From October 1984 to December 1998, 86 patients have been treated with prostate carcinoma. It was considered of Low risk those patients with PSA < or = 10 ng/ml, Gleason = 6 or stage T1-T2. Moderate risk: those with one elevated of the three parameters. High risk: two or more parameters. The treatment was carried out in a lineal accelerator using photons of 15 MV, with standard technique and frationation, administering a median dose of 66 Gy (58-75 Gy). It was defined disease free of recurrence (DFR), the time to clinical PSA or biochemical failure. This one was defined as the time starting from the date of nadir PSA to the second consecutive increase of PSA value after three separate serial measurements separated for at least one month. RESULTS: The median of initial PSA value was of 16 ng/ml (1-270), initial clinical stage T1-T2 (70p), stages T3-T4 (14p), and unknown in 2p. The median of Gleason score was 6 (2-10). According to the group of risk they were classified as: low risk in 16 patients (19%), moderated risk in 22 patients (26%), high risk in 21 patients (24%), and unknown in 27 patients (31%). Median nPSA value was 0.8 ng/ml (limits: 0-139) and the median time elapsed between the initial PSA and nPSA has been of 11 months (limits: 0-72 months). The actuarial DFR projected to five years in those patients with nPSA = 1 ng/ml was of 67% vs. 47% in patient with nPSA figures > 1 ng/ml (p = 0.0018). The PFD in patients with time to nadir (t nadir) < 12 months it was of 20% vs. 80% in patients with t nadir > 12 months (p < 0.0001). Multivariate analysis demonstrated that time to nadir (H.R: 0.11 p = 0.001), group of risk (H.R: 28.72 p = 0.020), and grade of differentiation (HR: 28.72 p = 0.010), were determinant to DFR. CONCLUSIONS: nPSA is an important factor to determine the objective response to radiotherapy. nPSA and time to nadir are prognostic factors that influences significantly on the DFR. The indication of adjuvant treatment in those patients with unfavorable prognostic factors such us those who do not reach nadir PSA < or = 1 ng/ml and time to nadir < or = 12 months, deserves the realization of a prospective study.

Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer.

PURPOSE: Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. TS gene promoter possesses regulatory tandemly repeated (TR) sequences that are polymorphic in humans, depending on ethnic factors. These polymorphisms have been reported to influence TS expression. TS expression levels affect tumor downstaging after preoperative fluoruracil (5-FU)-based chemoradiation. Tumor downstaging correlates with improved local control and disease-free survival. The aim of this study is to correlate TR polymorphisms with downstaging and disease-free survival. PATIENTS AND METHODS: Sixty-five patients with rectal cancer underwent tumor resection after preoperative 5-FU-based chemoradiation. Tumor downstaging was evaluated by comparing the pretreatment T stage with the pathologic stage observed in the surgical specimen. TS polymorphism genotype was determined by polymerase chain reaction amplification of the corresponding TS promoter region, and products of amplification were electrophoresed, obtaining products of 220 bp (2/2), 248 bp (3/3), or both (2/3). The TS polymorphism genotype results were subsequently compared with the downstaging observed and with disease-free survival. RESULTS: Patients who were homozygous for triple TR (3/3) had a lower probability of downstaging than patients who were homozygous with double TR or heterozygous patients (2/2 and 2/3): 22% versus 60% (P =.036; logistic regression). Furthermore, a trend toward improved 3-year disease-free survival was detected in the 2/2 and 2/3 groups, compared with that in the 3/3 group (81% v 41%; P =.17). CONCLUSION: This preliminary study suggests that TS repetitive-sequence polymorphisms are predictive for tumor downstaging. TR sequences in TS promoter may be useful as a novel means of predicting response to preoperative 5-FU-based chemoradiation.

Long-term normal tissue effects of intraoperative electron radiation therapy (IOERT): late sequelae, tumor recurrence, and second malignancies.

PURPOSE: To evaluate long-term survivors treated with intraoperative electron radiation therapy (IOERT) as a component, with particular emphasis on analyzing late normal tissue toxicity, second malignancies, and patterns of delayed tumor recurrence. METHODS AND MATERIALS: From September 1984 to December 1991, 739 patients were treated with IOERT. One hundred ninety-five patients were alive at least 5 years after IOERT (26%). Patient information regarding late complications related symptoms, incidence of second tumors, and delayed relapses were analyzed. Normal tissue changes were categorized by a modified LENT/SOMA scale (Grade 0-1, Grade 2, and Grade 3-4). Risk of late toxicity was grouped by type and number of cancer treatment modalities employed in each patient: surgery + IOERT alone (17 patients, 9%); IOERT + external radiotherapy +/- chemosensibilization (90 patients, 46%); IOERT +/- external radiotherapy +/- neoadjuvant chemotherapy (+/- previous radiotherapy) (88 patients, 45%). Biologic effective doses (BED) were calculated for alpha/beta = 3.5 for late fibrosis. RESULTS: With a mean follow-up time of the surviving patients of 94 months (range: 55-162 months), 99 patients (51%) had Grade 0-1 toxicity, 52 (27%) had Grade 2, and 44 patients (23%) presented Grade 3-4 late normal tissue complications. Risk groups by treatment intensity did correlate with severity of observed toxicity (p < 0.001). BED estimations did not correlate with late normal tissue damage. The tumor type with higher toxicity scores was bone sarcoma (28/46, 60%), in which the estimated BED = 100.5 Gy. Peripheral neuropathy was the dominant IOERT-specific toxicity present in 24 patients (12%). Second malignancies were identified in 8 patients (4%), none inside the IOERT field (3 questionable to be marginal to the external beam radiotherapy volume). In 36 patients (18%), recurrence of the originally treated tumor was detected, including 11 (7%) local relapses. CONCLUSIONS: The incidence of late normal tissue complications (50%) and severity (23%) is significant in a cohort of patients surviving more the 5 years after IOERT. The understanding of the contribution of IOERT to late tissue damage requires specific analysis. Peripheral neuropathy is a characteristic finding in IOERT trials. Second malignancies inside the IOERT field were not identified during the study period. The risk of recurrences, including local failures, requires an intensive follow-up of long-term survivors from IOERT trials.

Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.

BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.

[Intraoperative radiotherapy with accelerated electrons for urinary bladder carcinoma: principles and results]. / Radioterapia intraoperatoria con electrones acelerados en el carcinoma de vejiga urinaria: fundamentos y resultados.

OBJECTIVE: To describe intraoperative radiotherapy with accelerated electrons, a highly selective method of administering irradiation for radical treatment of bladder cancer. METHODS: We reviewed the experience reported in the literature since this treatment modality was utilized in Japan and its application extended to the western countries. RESULTS: Animal experiments have shown an acceptable clinicopathological tolerance to 20 Gy intraoperative irradiation of partial bladder volume. The local recurrence rate was 9% for early solitary tumor (> T2) and 27% for early multicentric tumor, according to the Japanese clinical experience. In the western countries, intraoperative radiotherapy plus external irradiation with or without systemic chemotherapy achieves a pT0 of about 65% (in total cystectomy specimens) and an intravesical tumor control rate of 88% in organ-sparing protocols. CONCLUSIONS: The results achieved by the groups with wider experience demonstrate that highly selective intraoperative radiotherapy is feasible, well-tolerated and effective in terms of inducing complete pathological remissions and definitive control of intravesical tumor. These selected clinical experiences must be corroborated by multicenter studies.

Pilot study of concurrent cisplatin, 5-fluorouracil, and external beam radiotherapy prior to radical surgery +/- intraoperative electron beam radiotherapy in locally advanced cervical cancer.

PURPOSE: The purpose of this study was to describe the feasibility of a combined preoperative chemoradiation program followed by radical surgery in advanced cervical cancer. MATERIALS AND METHODS: From February 1988 to April 1997, 40 patients with carcinoma of the cervix were treated with preoperative external beam radiotherapy to 45 Gy in 5 weeks. Patients received concurrent continuous infusion cisplatin (20 mg/m2) and 5-fluorouracil (1500 mg) chemotherapy during the first (days 1-4) and fifth (days 22-25) weeks of the radiation course. Radical surgery was performed 4-6 weeks after the completion of the preoperative treatment. Intraoperative radiotherapy was given to 20 patients, based on intraoperative assessment. RESULTS: Toxicity associated with chemoradiation was usually mild except in two patients who presented WHO grade 4 bone marrow aplasia. Three patients developed postoperative ureterovaginal fistula, and five patients developed long-term hydronephrosis that needed ureteral stenting. Clinical response was observed in 95% of the patients (55% complete response). The analysis of the surgical specimens revealed complete pathological response in 67.5% of the cases and partial pathological response in 32.5%. As expected, the degree of pathological response was predicted by the degree of clinical response (P = 0.001). Nine-year local control, distant metastases-free survival, disease-free survival, and overall survival were 86, 84, 81, and 85%, respectively. Patients displaying a complete pathological response had statistically significant improved local control (P = 0.004), distant metastases-free survival (P = 0.009), disease-free survival (P = 0.002), and overall survival (P = 0.038). CONCLUSIONS: Cisplatin plus 5-fluorouracil preoperative chemoradiation is active and usually well tolerated in locally advanced carcinoma of cervix, inducing a high rate of clinical and pathological complete responses. When this therapy is followed by radical surgery, the local control rates are excellent, even in patients with advanced stages or poor response. These improved local control rates may be achievable only through extensive surgical resection, with a parallel increase in the complication rates.

Induction platinum-based chemotherapy followed by radical hyperfractionated radiotherapy with concurrent chemotherapy in the treatment of locally advanced non-small-cell carcinoma of the lung.

This study evaluated tolerance, local control, and short-term survival in patients with locally advanced non-small-cell lung carcinoma treated with induction chemotherapy followed by radical hyperfractionated radiotherapy with concurrent chemotherapy. Thirty-one patients with stage IIIa (N2) or IIIb tumors were treated with cis-platinum-based induction chemotherapy for 1 to 4 courses followed by radical hyperfractionated radiotherapy (69.6 Gy) with concurrent chemotherapy given at the beginning and end of radiotherapy. Induction chemotherapy produced no complete responses and 18 (58%) partial responses. After completion of radiotherapy, 4 patients had complete response (13%) and 23 patients (74%) partial response. The patterns of failure were as follows: intrathoracic, 6 patients (22%); intrathoracic + distant metastasis, 6 patients (22%); distant metastasis without thoracic failure, 5 patients (19%). Six patients of the 12 with intrathoracic failure experienced in-field radiotherapy pure local failure. At the time of this analysis, 10 patients were alive and well (4 complete and 6 partial responders). Actuarial survival projected at 39 months is 35%. No benefit was observed for those patients responding to induction chemotherapy. Toxicity was as follows: grade III neutropenic fever in 4 patients (13%), grade IV neutropenia in 13 patients (42%), pneumonia in 6 patients (19%), grade III esophagitis in 4 patients (13%) and severe clinical pneumonitis in 1 patient (3%). Induction chemotherapy followed by chemoradiotherapy is feasible, and the preliminary results are encouraging. Complete response after radiotherapy appeared to be related to short-term disease-free survival, and decisions based on the response to chemotherapy may be equivocal.

[Positron emission tomography with F-18-FDG: a new tool in the evaluation of patients with head and neck tumors]. / Tomografía de emisión de positrones con F-18-FDG: una nueva técnica en la evaluación de pacientes con neoplasias de cabeza y cuello.

INTRODUCTION: Positron emission tomography using fluoro-deoxyglucose (PET-FDG) imaging has been shown to be effective in detecting and staging malignancies based on tumor glucose metabolism. The aim of the study was to evaluate the use of PET-FDG for the detection of metastatic lesions as well as early recurrence in patients with head and neck tumors. MATERIAL AND METHODS: Eleven patients were examined with PET-FDG to study the reliability of PET in assessing regional nodal status and in identifying distant metastasis (group I) and 37 patients who had previously received curative treatment and who presented differential diagnostic problems were imaged to differentiate between scar and residual or recurrent cancer (group II). PET-FDG studies were compared to results of computed tomography (CT) in 35 patients, magnetic resonance imaging (MRI) in 4 patients and both techniques in 6 patients. RESULTS: All PET-FDG studies were positive in group I, while CT failed to detect metastatic lesions in three patients. In group II PET-FDG accurately detected recurrent disease in 22/25 patients, while CT/MRI were negative in 4 cases and equivocal in 6 cases. However, there was a false positive PET study with equivocal CT in a patient with local infection. CONCLUSION: PET-FDG was highly effective in detecting metastatic cervical lymph nodes in head and neck tumours. It was most helpful in differentiating residual or recurrent tumour from scar sequelae and it enhanced the diagnostic accuracy when CT and MRI were equivocal due to anatomical distortions.

Preoperative chemotherapy followed by esophagectomy compared with surgery alone in the treatment of squamous cell carcinoma of the esophagus.

The aim of this study is to assess the effect of concomitant preoperative radio-chemotherapy in the treatment of epidermoid esophageal cancer. We studied a total of 45 patients, divided into two groups. Group I consisted of 20 patients diagnosed with epidermoid esophageal cancer who had been treated initially with esophagectomy. Group II consisted of 25 patients treated with preoperative radiotherapy and two cycles of chemotherapy (cisplatin and 5-fluorouracil), one at the beginning and the other at the end of the radiation treatment, on whom an esophagectomy was subsequently performed. The clinical characteristics were similar in both groups. In group II, there were 12 cases (48%) with absence of tumor in the esophageal wall, three of which had node involvement. The operative mortality was similar in both groups (10% and 8% respectively). The only significant difference found in the postoperative complications was the incidence of anastomotic leak; but this was related to the different esophagectomy techniques used rather than the type of therapy. A decrease in the number of patients with tumor recurrence was observed in Group II, especially where the local component was concerned. The best actuarial survival rate at five years was in patients with no presence of tumor after neoadjuvant treatment (44.4%). However, the radio-chemotherapy seems not to have had any benefit in cases with node involvement.

Intraoperative radiotherapy. Literature updating with an overview of results presented at the 6th International Symposium of Intraoperative Radiation Therapy.

Intraoperative radiotherapy is a technique that can be integrated into multidisciplinary treatment strategies in oncology. A radiation boost delivered with high energy electron beams can intensify locoregional antitumor therapy in patients undergoing cancer surgery. Intraoperative radiotherapy can increase the therapeutic index of the conventional combination of surgery and radiotherapy by improving the precision of radiation dose location, while decreasing the normal tissue damage in mobile structures and enhancing the biological effect of radiation when combined with surgical debulking. Intraoperative radiotherapy has been extensively investigated in clinical oncology in the last 15 years. Commercially available linear accelerators require minimal changes to be suitable for intraoperative radiotherapy. Its successful implementation in clinical protocols depends on the support given by the single institutions and on a clinical research-oriented mentality. Tumors where intraoperative radiotherapy as a treatment component has shown promising rates of local control include locally advanced rectal, gastric and gynecologic cancer, bone and soft tissue sarcoma. Intraoperative radiotherapy can be applied to brain tumors, head and neck cancer, NSCLC and pancreatic carcinoma.

Chemoradiation followed by surgery: its role in local control in advanced cervical cancer.

The aim of this study was to improve local control and consequently survival, by using chemoradiation followed by surgery. After a median follow-up of 57+ months, 95% CI (9-111) five year overall survival (OS) was 81.8%, 90% and 85.7% in stage Ib2-IIa bulky, IIb and III-IVa, respectively (p = NS). Disease-free survival (DFS) was 81.8% 80% and 71.4% (p = NS) and disease-free survival of local failure (DFSLF) was 95.4%, 80% and 100% (p = NS) for stage Ib2-IIa, bulky, IIb and III-IVa respectively. Distant metastases were present in every group, ranging from 13.6% to 17% in the early bulky and advanced groups respectively. Pathologic findings revealed complete response (CR) (no residual disease or scattered microscopic tumoral foci) in 27/40 (67%), and partial response (PR) in 11/40 (27%). According to the pathologic response, DFS was 92.6% and 50% (p = 0.0029) and DFSLF was 100% and 77.8% (p = 0.0127) in complete and partial response respectively. This therapeutical approach promoted a high rate of pathologic complete response (PCR) PCR as well as of local control in this group at high risk for recurrence.

Patterns of failure and long-term results in high-risk resected gastric cancer treated with postoperative radiotherapy with or without intraoperative electron boost.

BACKGROUND: To evaluate the possible role of adjuvant radiotherapy in the management of high-risk resected gastric carcinoma. METHODS: From 1982 to 1993, 62 patients surgically resected of a primary gastric cancer with adverse pathological features (serosal and/or regional lymph node involvement) were treated with postoperative radiotherapy with (Group I) or without (Group II) intraoperative electron boost to the surgical bed and coeliac axis (IORT). RESULTS: After a median follow-up of 75.6 months (range 4-120+) for IORT patients and 91.2 months (range 6-149+) for non-IORT patients, overall relapse rates for Group I and Group II patients were 44.5% and 48.6% and local-regional relapse rates were 11.1% and 20%, respectively. Actuarial survival rates projected at the maximum follow-up were 41% and 38% in Groups I and II, respectively. CONCLUSIONS: This retrospective analysis suggests a beneficial effect of adjuvant external radiotherapy in promoting local-regional control in high-risk resected gastric cancer.