Laryngeal preservation in head and neck cancer: multidisciplinary approach

Since the first total laryngectomy was undertaken, efforts have been made to avoid removing the entire larynx. For a long time, partial surgery and radiotherapy were the only options that could preserve the larynx. Development of active chemotherapy regimens has prompted an era of intensive clinical research. Induction chemotherapy followed by radiotherapy in patients with objective responses has been shown to allow conservation of the larynx in nearly two-thirds of individuals, without any effect on survival; concurrent chemoradiotherapy also provides high rates of laryngeal preservation, again without affecting survival; and induction chemotherapy followed by concurrent chemoradiotherapy is under investigation. In the meantime, partial open surgery and endoscopic carbon dioxide laser procedures are feasible in selected moderately advanced laryngopharyngeal cancers as an alternative to destructive surgery. Altered fractionation radiotherapy can also be used in management of these tumours, and targeted treatments have opened a new area of clinical research. Findings of basic research and modern imaging should provide useful approaches for selection of patients for various strategies.     

Functional Organ Preservation in Locally Advanced Laryngeal Squamous Cell Carcinoma: Is there a Role for Induction Chemotherapy?

Concurrent chemoradiation (CRT) is currently the most effective strategy for organ preservation in locally advanced laryngeal squamous cell carcinoma (SCC) unsuitable for function-preserving surgery. The larynx preservation approach of induction chemotherapy followed by radiotherapy in responders is based on the hypothesis that tumours that show a satisfactory response to induction chemotherapy are more likely to respond to radiation-based treatment. This enables the use of chemotherapy response to identify patients who are more likely to achieve long-term disease control with organ-preserving therapies. An induction chemotherapy response allows prognostication, outcome prediction and treatment selection in patients with locally advanced laryngeal SCC. Excellent survival outcomes have been achieved with induction chemotherapy followed by CRT as definitive therapy in responders. The addition of docetaxel to cisplatin and 5-fluorouracil induction chemotherapy has also resulted in higher larynx preservation rates. Future organ preservation studies should assess whether induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil followed by CRT in responders improves survival compared with an unselected approach of primary CRT in all eligible patients with T2 or T3 laryngeal SCC. The primary end point of such studies should be laryngo-oesophageal dysfunction-free survival, which focuses on the treatment goals of survival, disease control and laryngeal–oesophageal function after therapy. In addition, the inclusion of patients with N2 or N3 disease will help to determine whether the addition of docetaxel, cisplatin and 5-fluorouracil to CRT reduces the incidence of distant relapse in advanced laryngeal SCC. Other areas of interest include the use of concurrent cetuximab in place of platinum-based chemotherapy with radiotherapy in larynx preservation and the search for better predictive markers of successful larynx preservation than induction chemotherapy response.     

Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891

BackgroundWe report the 10-year results of the EORTC trial 24891 comparing a larynx-preservation approach to immediate surgery in hypopharynx and lateral epilarynx squamous cell carcinoma.Material and methodsTwo hundred and two patients were randomized to either the surgical approach (total laryngectomy with partial pharyngectomy and neck dissection, followed by irradiation) or to the chemotherapy arm up to three cycles of induction chemotherapy (cisplatin 100 mg/m² day 1 + 5-FU 1000 mg/m² day 1–5) followed for complete responders by irradiation and otherwise by conventional treatment. The end points were overall survival [OS, noninferiority: hazard ratio (preservation/surgery) ≤ 1.428, one-sided α = 0.05], progression-free survival (PFS) and survival with a functional larynx (SFL).ResultsAt a median follow-up of 10.5 years on 194 eligible patients, disease evolution was seen in 54 and 49 patients in the surgery and chemotherapy arm, respectively, and 81 and 83 patients had died. The 10-year OS rate was 13.8% in the surgery arm and 13.1% in the chemotherapy arm. The 10-year PFS rates were 8.5% and 10.8%, respectively. In the chemotherapy arm, the 10-year SFL rate was 8.7%.ConclusionThis strategy did not compromise disease control or survival (that remained poor) and allowed more than half of the survivors to retain their larynx.     

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.     

Candidates for larynx preservation: the next step?

Nonsurgical treatment approaches to enable larynx preservation in patients who would otherwise undergo laryngectomy have evolved over recent years. Randomized trials have demonstrated that concurrent chemotherapy and radiotherapy is more effective than doublet cisplatin and 5-fluorouracil (5-FU) (PF)-based induction chemotherapy and radiotherapy in enabling larynx preservation. However, concurrent chemotherapy and radiotherapy is also associated with more toxicities than induction PF followed by radiotherapy. The triplet induction regimen of docetaxel, cisplatin, and 5-FU (TPF) is more effective than PF and is now considered to be the standard induction chemotherapy regimen for future larynx preservation trials. Manipulating the postinduction treatment regimen may help to improve larynx preservation rates, and possibly survival, and the use of concurrent chemoradiotherapy and radiotherapy plus the epidermal growth factor receptor inhibitor cetuximab has been investigated in this setting. Determining the most effective treatment approach for larynx preservation will involve conducting a trial comparing concurrent chemotherapy and radiotherapy with sequential TPF induction chemotherapy followed by either radiotherapy or cetuximab plus radiotherapy. Collaboration among international groups is required to assess which approach would be most beneficial in terms of larynx function preservation, disease control, and survival.     

Induction chemotherapy and larynx preservation: is such practice useful?

BACKGROUND: Surgery followed by irradiation is considered to be the standard treatment but require frequently a total laryngectomy. Chemotherapy followed by irradiation is available in larynx and hypopharynx squamous cell carcinoma (SCC) treatment. Are results obtained in daily induction chemotherapy usefulness identical to results obtained in larynx preservation studies? PATIENTS AND METHOD: We conducted a retrospective study on patients treated at centre Oscar-Lambret, Lille, from 1986 to 1995, by chemotherapy followed by definitive radiotherapy or by surgery and radiotherapy for laryngeal or hypopharyngeal cancer treatment. All patients were naive of previous head and neck SCC and a surgical treatment, requiring total laryngectomy, should be proposed with curative intent. Induction chemotherapy associated cisplatin (100 mg/m2) on day 1 and 5-fluorouracil (5FU)(1,000 mg/m2) on days 1-4 or 1-5. Irradiation was performed for responders (complete or partial > 50%). If case of non-responder, patients underwent surgical treatment followed by irradiation. We compared results obtained with patients enrolled in clinical trial and with patients whom benefited from this protocol out of trial. RESULTS: Hundred-eight patients were evaluable for purposes of this study. Fifty-two patients were included in clinical trial (group 1) while 56 patients (group 2) were not. There was no statistical difference as regard neither to sex nor to node (palpable or not palpable) and metastasis status between the groups. We found a higher frequency of laryngeal tumour in group 2 (31 vs 17; p =.03). We observed more stage III and less stage IV in group 1. For chemotherapy-related toxic reactions, the exclusive statistical difference observed was haematological toxicity grade III and IV after the second cycle (0 pt in group 1 vs 8 pts in group 2; p =.02). After initial treatment, complete response was achieved without statistical difference between the groups (88.2% vs 78%; p =.27). A surgical procedure was performed in 46 cases without difference according to the reference group and functional larynx preservation was 55.8% (29/52) in group 1 and 53.6% (30/56) in group 2. Whatever the group, causes of death were similarly distributed. Cancer was the first cause of death in both groups. The overall survival of the population (108 patients) was 81.5% at one year, 49.6% at 3 years and 35.3% at 5 years with a median survival of 3 years. There was no statistical difference between both groups. Some parameters influenced the overall survival like T (p =.04), response to chemotherapy (p=.006), extra capsular spread (p = 0.03) and response after completion treatment. CONCLUSION: Induction chemotherapy is available for larynx preservation but cannot be considered as a standard treatment. Nevertheless, results should be reproduced in daily practice with experimented teams as found with non included patient's results. The long-term side effects of such protocols should be evaluated. Recent publication, on increase postoperative infection after chemotherapy, should be evaluated in clinical trial. If confirmed, cost effectiveness of such complication must be integrated in larynx preservation protocols. Larynx preservation remains an interesting point of view for patients but stay an optional procedure and not a reference.     

TPF: a rational choice for larynx preservation?

For many years, the standard approach for the treatment of resectable squamous cell carcinoma of the head and neck was surgery, with or without subsequent radiotherapy. However, the morbidity associated with this approach, particularly for patients requiring total laryngectomy, can severely impair a patient's quality of life. The finding that patients whose tumors responded to chemotherapy showed a good response to subsequent radiotherapy opened up the possibility of a new organ-preserving management strategy for patients with resectable disease. Randomized studies demonstrated that induction chemotherapy with a cisplatin-5-fluorouracil (5-FU) doublet (PF) prior to radiotherapy enabled larynx preservation in a substantial proportion of patients, compared with surgery plus radiotherapy, without compromising survival. The benefit in terms of larynx preservation when using platinum-based doublet induction chemotherapy followed by radiotherapy, compared with concurrent chemotherapy and radiotherapy, is less clear, although the sequential approach appears to be better tolerated. Adding the taxane docetaxel to PF, to create the TPF triplet regimen, led to significantly higher larynx preservation and laryngectomy-free survival rates than with the PF doublet. TPF is now the accepted standard induction chemotherapy regimen for future clinical trials in resectable disease. Methods for improving postinduction treatment strategies are being explored.     

Quimioterapia de inducción seguida de radioquimioterapia como alternativa a la laringuectomía en el tratamiento del cáncer de cabeza y cuello localmente avanzado

Objective

To evaluate survival in patients with loco-regional advanced head and neck cancer treated with induction chemotherapy and to assess possible larynx preservation in good responders.

Materials and methods

Between December 1997 and June 2000, patients (n=46) diagnosed as having advanced head and neck carcinoma were treated with induction chemotherapy (CT). This was followed by radiotherapy (RT) + CT if there had been complete response (CR) or partial response (RP) >80%; or followed by total laryngectomy and adjuvant RT if CR or PR was <80%.

Results

Of the 46 patients studied, 57 (80%) had CR, 10% had PR and 10% had no response or disease progression (DP). Median survival was 33%, followup was of 50 months during which the overall survival was 36%, disease-free survival (DFS) was 60% and loco-regional control was 51%.

Conclusion

RT-CT resulted in high rates of disease resolution and speech preservation in patients who, traditionally, had poor clinical and functional outcomes.     

Cetuximab in the management of locoregionally advanced head and neck cancer: Expanding the treatment options?

The treatment of locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) has evolved in recent years as a consequence of a better understanding of the potential benefits associated with altered radiation fractionation regimens, concurrently administered chemotherapy and radiotherapy (chemoradiotherapy) and induction chemotherapy. Concurrent chemoradiotherapy is a treatment option for technically resectable disease, where functional morbidity precludes the use of surgery. Induction chemotherapy followed by radiotherapy may also be used in this setting, and has been validated for larynx preservation. Concurrent chemoradiotherapy is a standard treatment approach for medically fit patients with locoregionally advanced unresectable disease. However, the toxicity burden of additional chemotherapy in both the concurrent chemoradiotherapy and induction chemotherapy settings can have implications for treatment compliance and may impede the administration of chemotherapy and/or radiotherapy to schedule. The epidermal growth factor receptor (EGFR)-targeted IgG1 monoclonal antibody, cetuximab (Erbitux®), has shown significant clinical benefits in the treatment of both locoregionally advanced and recurrent and/or metastatic SCCHN. A phase III study in locoregionally advanced disease demonstrated significant improvements in locoregional control and progression-free and overall survival with cetuximab plus radiotherapy compared with radiotherapy alone, and overall survival benefits were maintained at 5 years. The addition of cetuximab to concurrent chemoradiotherapy has been shown to be feasible in phase II trials and is being investigated in phase III trials. Preliminary evidence suggests that cetuximab could be incorporated into induction management strategies. Taken together, these data support an important role for cetuximab in the treatment paradigm for locoregionally advanced SCCHN.     

Advanced carcinoma of the larynx: Results of surgery and radiotherapy without induction chemotherapy (1980–1985): A multivariate analysis

Induction chemotherapy has been proposed in the case of advanced laryngeal cancer in order to preserve laryngeal function in those patietns who are complete responders. To clarify the treatment policies, a restrospective multicentric analysis of 116 patients with advanced carcinoma of the larynx treated by radical surgery and postoperative radiotherapy was carried out in order to evaluate prognostic factors for local control and survival.

Between 1980 and 1985, 116 patients with Stage III squamous cell carcinoma of the larynx underwent radical surgery and postoperative radiotherapy with a curative intent. Treatments were very homogenous, and doses delivered were in the range of 50–65 Gy according to nodal involvement and surgical margins status.

The local recurrence rate and the local disease-free survival rate at 5 years were 22.5% and 76.3%, respectively. Actuarial survival at 5 years was 68.3% with 44 patients stil alive who no evidence of disease (NED) with more than 5 years follow-up. For both overall survival and relapse-free survival, cervical node involvement with capsular rupture was found to be the only significant adverse pronostic factor in univariate and multivariate analysis. No other parameter was predictive either for local recurrence or for survival.

Local prognosis and survival depend largely on nodal involvement and capsular rupture while increasing doses of radiation strategy is likely to reduce the risk of local and nodal recurrence. Preservation of functional larynx is certainly an important goal to achieve when treating advanced carcinoma of the larynx, provided that local failure rate and survival be similar. In the unique randomized study previously published in the literature comparing radical surgery and postoperative radiotherapy to induction chemotherapy and radiotherapy, the local-regional failure rate was drastically increased in the chemotherapy arm. Other results from well-designed controlled studies are awaited before recommending systemic induction chemotherapy and larynx preservation in complete responders. On the other hand, testing synchronous or alternated chemotherapy vs. induction chemotherapy may address the pending questions about the optimal treatment of advanced laryngeal carcinoma.     

Concurrent chemoradiotherapy versus induction chemotherapy followed by chemoradiotherapy (sequential approach) in the management of head and neck cancer

Concurrent chemoradiation is considered the standard-of-care for locally advanced head and neck cancer of the hypopharynx, oropharynx and larynx, as well as unresectable disease. This paradigm was challenged by the introduction of induction chemotherapy (IC), which demonstrated non-inferiority in regards of overall survival (OS), along with increased organ preservation, when compared to the surgery and radiotherapy. More recently, IC followed by concurrent chemoradiation, the so-called sequential approach was developed in an attempt to decrease metastatic spread and improve locoregional control (LRC) rates, with much controversy amongst experts. A careful evaluation by a multidisciplinary team is necessary to recognize which patients should be offered this therapeutic approach due to a significantly greater rate of toxicity. Herein, we analyze the most current available evidence regarding the use of sequential therapy versus concurrent chemoradiation. Different factors including toxicity profile, adherence and patient characteristics play a major role in choosing the most appropriate treatment regimen.     

Localized childhood Hodgkin's disease: response-adapted chemotherapy with etoposide, bleomycin, vinblastine, and prednisone before low-dose radiation therapy-results of the French Society of Pediatric Oncology Study MDH90.

PURPOSE: The French Society of Pediatric Oncology MDH82 study demonstrated the effectiveness of 20 Gy irradiation of involved fields after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, vincristine, procarbazine, and prednisone/ABVD chemotherapy in children with localized Hodgkin's disease (HD). The response to primary chemotherapy was the only predictor of survival. To reduce long-term treatment complications without compromising efficacy, the MDH90 study was based on a new chemotherapy regimen devoid of both alkylating agents and anthracycline, followed by 20 Gy of radiotherapy (RT) for good responders. PATIENTS AND METHODS: From January 1990 to July 1996, 202 children were enrolled from 30 institutions. Good responders to four cycles of vinblastine, bleomycin, etoposide (VP16), and prednisone (VBVP) were given 20 Gy of RT and no further therapy. Poor responders were given vincristine, procarbazine, prednisone, and doxorubicin. After a second evaluation, good responders were given 20 Gy of RT, and poor responders were given 40 Gy of RT. RESULTS: One hundred seventy-one patients (85%) were good responders to VBVP, 27 (15%) were poor responders, and four did not respond. With a median follow-up of 74 months (range, 25 to 117 months), the 5-year overall survival rate (mean +/- SD) is 97.5% +/- 2.1%, and the event-free survival rate (mean +/- SD) is 91.1% +/- 1.8%. Significant predictors of worse event-free survival in multivariate analysis were hemoglobin < 10.5 g/L, "b" biologic class, and nodular sclerosis. CONCLUSION: These results suggest that most children with clinical stage I and II HD can be treated with chemotherapy devoid of alkylating agents and anthracycline, followed by low-dose RT.     

Radiation Therapy With 5-fluorouracil in Head and Neck Cancer

5-Fluorouracil (5-FU) alone or combined with other drugs, most frequently cisplatin, has been used concurrently or as induction or adjuvant therapy with radiotherapy with or without surgery in the treatment of head and neck cancer. Improved local-regional control and disease-free survival or overall survival have been shown in several randomized trials using a concurrent approach. However, acute mucositis is usually increased with simultaneous 5-FU and radiation administration, especially when other drugs are used in addition to 5-FU. Alternating radiotherapy with 5-FU and cisplatin was shown to improve the local-regional relapse-free, progression-free, and overall survival of unresectable squamous cell carcinoma of the head and neck compared with radiotherapy alone in one randomized trial. Further evaluation of the alternating chemotherapy and radiotherapy approach is needed, however, before one can accept this as a standard of practice. Induction chemotherapy with 5-FU infusion and cisplatin followed by definitive radiotherapy in the chemotherapy responders in an alternative treatment option for patients with locally advanced resectable squamous cell carcinoma of the larynx or hypopharynx who wish to preserve organ function. Induction or adjuvant chemotherapy with 5-FU infusion and cisplatin may also decrease or delay the occurrence of distant metastasis. Induction chemotherapy, however, has not been shown to improve local-regional control or overall survival. Further clinical trials combining 5-FU and its biochemical modulators using innovative radiation and drug dose schedules and other treatment modifiers are needed to improve the therapeutic ratio.     

Glottic laryngeal carcinoma with fixed vocal cord treated with full-dose radiation, total laryngectomy or combined treatment

The results of the therapy of 46 patients with glottic squamous cell cancer with a fixed vocal cord and without regional lymph nodes (glottic T3N0) are reported. Primary surgery (total laryngectomy) in combination with preoperative irradiation gave significantly higher loco-regional control rate and survival rate than surgery alone. Primary radiotherapy with doses of 70 Gy or more and adequate follow-up was found to be an alternative to preoperative radiation and laryngectomy. The result of different treatment modalities speaks in favour of primary irradiation allowing preservation of the larynx and a good voice function. In case of recurrence salvage surgery with total laryngectomy is preferred.     

Concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma

Early glottic carcinoma has a good prognosis compared to other head and neck carcinomas, but we must aim for larynx preservation in the treatment. Regarding T1N0, larynx preservation rates are favorable even with radiotherapy alone. However for T2N0, the treatment strategies differ in each institution, and larynx preservation rates range from 72% to 85%, and are not high enough. We conducted a study to determine the efficacy of the concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma. In this study, 12 patients with T2N0 glottic type laryngeal squamous cell carcinoma enrolled from the year 2004 to 2006, received one reduction dose of S-1 (80 or 100 mg/day) with concomitant irradiation with a total dose of 60-70 Gy (2.0 Gy/fr). The 2-week administration of S-1 followed by one-week rest was repeated during irradiation. In terms of adverse events of Grade 3 and above, Grade 3 mucositis and dermatitis were found in 2 patients each, but there was no cancellation nor interruption of S-1 or irradiation. All patients achieved pathological CR at the time of evaluation after the primary treatment, and no recurrences have been seen yet in any of the primary sites. Concurrent chemoradiotherapy with S-1 showed efficacy in T2N0 glottis carcinoma. Further investigation of this treatment with long-term follow up results is warranted.     

Sequential induction chemotherapy and concomitant chemoradiotherapy in the management of locoregionally advanced laryngeal cancer

Purpose:To determine overall survival, progression-free survival,rate of voice preservation, and patterns of failure in locoregionally advancedlaryngeal cancer treated with induction chemotherapy with or without surgeryfollowed by concomitant chemoradiation. Background:Locoregionally advanced laryngeal cancer has beenconventionally treated with either surgery and adjuvant radiotherapy orradiotherapy alone, and clinical and functional outcomes have been poor.Chemoradiotherapy has been demonstrated to improve functional outcome anddisease control over conventional treatment in recent randomized head and necktrials. Patients and methods:Advanced head and neck cancer patients wereenrolled onto two consecutive phase II studies. Induction treatment consistedof three cycles of cisplatin, 5-fluorouracil (5-FU), leucovorin, andinterferon-2b (PFL-IFN) followed by surgery for residual disease.Surgical intent was to spare the larynx when possible. All patients thenproceeded to concomitant chemoradiation consisting of seven or eight cyclesof 5-FU, hydroxyurea, and a planned total radiotherapy dose of 7000 cGy(FHX). Results:A subset of thirty-two laryngeal cancer patients withpredominantly stage IV disease comprises the study group for this report.Clinical CR was observed in 59% of patients following inductiontherapy. The median follow-up was 63.0 months for surviving patients and 44.5months for all patients. At five years, overall survival is 47%,progression-free survival is 78%, and locoregional control is78%. No distant failures were observed. Voice preservation with diseasecontrol was 75% at five years. Only two total laryngectomies wereperformed during the course of treatment and follow-up. Treatment-relatedtoxicity accounted for two deaths. Conclusions:The addition of concomitant chemoradiotherapy toinduction chemotherapy for locoregionally advanced laryngeal cancer appearsto increase locoregional control and survival rates. PFL-IFN–FHXresulted in high rates of disease cure and voice preservation in a group ofpatients that has traditionally fared poorly in both clinical and functionaloutcome.     

Chemotherapy for head and neck cancer

Chemotherapy for head and neck cancer was initially used as a palliative treatment in advanced and/or recurrent disease. The overall response rate was about 30% but patient survival was sometimes short. It was also observed that complete responders had a significantly longer survival period than non-responders. Cisplatin-containing regimens including cisplatin plus 5-fluorouracil appear to be the most efficacious for this disease. In a large number of randomized trials, organ function preservation studies have shown the possibility of laryngeal preservation for T2 and T3 laryngeal and hypopharyngeal cancer. A survival benefit has been shown clearly in advanced nasopharyngeal cancer. Another survival prolongation has been demonstrated in cases of locally unresectable cancer in the oral cavity, pharynx, nose and paranasal sinus. Thus, we conclude that neoadjuvant chemotherapy can be effective in cases of locally unresectable cancer in the oral cavity, pharynx, and nose and paranasal sinus. In advanced N stage nasopharyngeal cancer, neoadjuvant chemotherapy plus adjuvant chemotherapy may be indicated. Advanced T stage nasopharyngeal cancer is a good candidate for concurrent chemoradiotherapy. For the aim of laryngeal preservation, neoadjuvant and/or concurrent chemoradiotherapy can be indicated for T2 and T3 laryngeal and hypopharyngeal cancer.     

临床N2期非小细胞肺癌治疗进展

临床N2期非小细胞肺癌(NSCLC)最佳治疗方案仍未确定,根治性同期化放疗为目前推荐的标准治疗方案.诱导化疗后同期化放疗并不优于标准的同期化放疗;术前新辅助化疗并未能提高总生存率,但新辅助同期化放疗后肺叶手术切除能提高总生存率.同期化放疗后继续巩固化疗作用仍有争论;吉非替尼或厄洛替尼维持治疗也未能带来生存受益.预防性脑照射仅能降低脑转移率,并未能提高总生存率.     

Chemoradiation in rectal squamous cell carcinoma: Bi-institutional case series

Background and purposePrimary rectal squamous cell carcinoma (SCC) is an uncommon disease. Early reports stated that surgery is the most effective treatment. However, recent publications suggest conservative strategy with chemoradiation provides satisfactory results.Patients and methodsWe have retrospectively studied the medical charts of 23 patients treated for a rectal SCC in two teaching hospitals in France between 1992 and 2013. Twenty-one patients received an exclusive chemoradiotherapy (CRT) and two a pre-operative CRT followed by a planned surgery. Patients received pelvic irradiation with a dose ranging from 36–45 Gy followed by a boost of 15–23 Gy. Twenty-two patients received a concurrent chemotherapy.ResultsAfter CRT, the rate of clinical complete response was 83%. With a median follow-up of 85 months, 5-year overall survival rate was 86%. Five patients presented with a relapse. The 5-year disease-free survival rate was 81%. The 5-year colostomy-free survival rate was 65%. Three patients (13%) presented with grade III–IV late rectal toxicity.ConclusionsAlthough retrospective, this is the largest cohort of patients treated with CRT for a rectal SCC. Exclusive CRT could result in high local control rate and prolonged survival in rectal SCC patients with a high rate of organ preservation.     

New tools in adjuvant breast cancer radiotherapy

During the last century management of breast cancer became increasingly less aggressive for small tumors. Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery (BCS) followed by adjuvant radiation therapy (RT). BCS plus adjuvant RT +/- systemic therapy has become the standard of care for women with early breast cancer. Advances in modern RT technology allowed significant increase in high precision of target definition. Intensity modulated radiation therapy (IMRT) and gating, under investigation in miscellaneous cancers, are also in development for breast-cancer patients. These techniques decrease radiation toxicities and could be useful in the setting of concurrent use of RT and new systemic therapies such as trastuzumab. Another advance in RT is the development of accelerated partial breast irradiation (APBI) as a new concept in the adjuvant setting for early-stage breast cancer. Intraoperative RT (IORT), immediate postoperative RT (interstitial brachytherapy or Mammosite device implantation) and delayed postoperative RT (external beam of photons or protons with 3D conformation) are under investigation. In this review, the role of modern whole breast irradiation is discussed, the rational of partial breast irradiation is argued and the different techniques are detailed.