Treatment of recurrent and advanced stage squamous cell carcinoma of the head and neck

Despite advances in our ability to safely treat patients with recurrent cancer of the upper aerodigestive tract, outcomes for retreatment are generally poor and the first chance to cure these patients remains the best chance. Thorough knowledge of the outlook and options for patients with recurrent disease is also of significance in choosing therapy for patients with newly diagnosed disease. This is especially true for newly diagnosed patients making the choice between surgery and nonsurgical ("organ-sparing") options, who need to know the outlook for salvage surgery, should they recur after radiation with or without concomitant chemotherapy. Salvage surgery is generally the best option for previously irradiated patients who are faced with resectable, recurrent disease. Unfortunately, the results of surgical salvage are generally poor for patients with advanced stage recurrence and for those who recur after treatment of advanced disease. The site of initial and recurrent disease is important. Surgical salvage is most effective for patients with recurrent laryngeal cancer, least effective for recurrent cancer of the pharynx, and is intermediate for recurrence in the oral cavity. Patients choosing nonsurgical treatment for newly diagnosed cancer of the pharynx cannot rely on salvage surgery in the event of recurrence. Reirraditation for patients who have failed initial treatment that included radiation therapy has been used at a number of institutions with some success. Experience using reirradiation with or without concomitant chemotherapy continues to evolve. Palliative chemotherapy is an option for most patients, but response rates are generally poor and of short duration, after failure of initial treatment that includes radiation therapy. The best approach for many patients and families who face advanced recurrent disease is honest but compassionate communication and supportive care with the help of a hospice organization.     

Recurrent cervical cancer

Opinion statement There are limited treatment options for patients with recurrent cervical carcinoma. Because of low response rates and a negligible impact on long-term survival, the use of chemotherapy in patients with unresectable recurrent disease should be considered palliative. Generally, radiation therapy in previously irradiated patients is considered palliative. For patients who develop recurrent disease after definitive surgery who have not received prior radiation therapy, salvage radiation therapy is the treatment of choice. Similarly, patients who have received definitive primary radiation therapy are candidates for surgical resection of their recurrence. However, there are specific criteria for surgical resection. Radical hysterectomy may be an option for the very rare patient with a small (<2 cm) centrally located recurrence in the cervix or vaginal fornices. However, for most patients, pelvic exenteration remains the only therapeutic option that offers the possibility of long-term survival. Patients who are candidates for exenteration are those with central local recurrences that have not extended to the pelvic sidewalls. The introduction of high-dose-rate intraoperative radiation therapy (HDR-IORT) combined with radical surgical resection has widened the scope of patients who may be offered surgery. Patients who in the past may not have been surgical candidates may benefit from radical surgical resection combined with HDRIORT. All patients who are surgically fit and have undergone previous radiation therapy should be considered for surgical resection for centrally located recurrences. Patients whose recurrences extend close to the pelvic sidewalls should be referred to centers where HDR-IORT is available.     

Surgical salvage therapy: abdominoperineal resection for recurrent anal carcinoma, metastasectomy of recurrent colorectal cancer, and esophagectomy after combined chemoradiation

This review highlights the advances in the salvage surgical therapies for recurrent disease after definitive therapy of anal carcinoma, colorectal cancer, including liver metastasectomy, and esophageal carcinoma treated primarily with chemoradiation. New diagnostic modalities, advances in neoadjuvant therapies for unresectable liver metastases, and, in addition, the importance of adjuvant hepatic arterial chemotherapy after curative liver resections are reviewed. Although chemoradiation is not the standard of care for esophageal cancer, salvage esophagectomy after such treatment is discussed. Definitive chemoradiation for squamous cell carcinoma of the anus has altered the role of surgical intervention to a salvage option instead of primary treatment. Although this is not yet the case for esophageal carcinoma, recent improved chemoradiation regimens have been reported by the French and Japanese, who use surgery for nonresponders. For recurrent colorectal carcinoma, including liver-only metastases, patients can be rendered disease free after surgical extirpation with evidence of improved survival. Appropriate surveillance in these patients may identify subsets of patients with disease amenable to resection.     

The role of interstitial brachytherapy with salvage surgery for the management of recurrent head and neck cancers

BACKGROUND: The role of interstitial brachytherapy (IBT) in the salvage surgical management of regional lymphatic metastases for head and neck cancer has not been defined to date. To further explore its therapeutic benefit in the management of head and neck squamous cell carcinoma, the authors reviewed their experience utilizing IBT at the M. D. Anderson Cancer Center. METHODS: A retrospective chart review of all patients who were received IBT for cervical recurrences of head and neck cancer was undertaken. Twenty-two patients were identified; all patients underwent neck dissection and intraoperative placement of afterloading catheters as part of the salvage treatment. Soft tissue reconstruction was performed when necessary. The duration and dosage of salvage brachytherapy was reviewed, and the overall disease-free survival rates were determined. RESULTS: All patients had been treated with external beam radiation therapy prior to recurrence, with an average dose of 65 grays (Gy), and 46% of patients had undergone prior neck dissection. The median time to regional recurrence after definitive treatment was 30 months. Soft tissue coverage of the surgical bed with a muscle flap, most commonly a pectoralis major flap, was performed in 19 of 22 patients. The median IBT dose was 60 Gy over a total duration of 4 days. Postoperative complications were few, and there were no perioperative deaths. Recurrences in the reirradiated necks occurred in 27% of patients. CONCLUSIONS: Regional recurrences are common after multimodality treatment for head and neck cancer and are challenging to manage. Although its role has not been defined clearly, salvage neck dissection with IBT is beneficial in the management of recurrent lymphatic metastases of upper aerodigestive tract carcinomas.     

Locoregional recurrence of ORL cancer: the place of surgery

Surgery of locoregional failures is mainly represented by salvage surgery after radiotherapy. Due to progress of radiotherapy, especially modification of fractionation and association with chemotherapy, the problem of salvage surgery is nowadays emphasized. Despite the reduction of postoperative mortality and morbidity by the use of myocutaneous flaps the complications are still frequent and the rehabilitation long and difficult. Oncologic results are disappointing too, especially in salvage surgery for oropharyngeal and hypopharyngeal tumors with less than a half of patients being candidates for salvage surgery and 5 year survival rates inferior to 30% in these patients. Laryngeal tumors are more favorable for salvage surgery but in the majority of the cases recurrences after radiotherapy require a total laryngectomy. The poor postoperative, functional and oncologic results after salvage surgery, especially in pharyngeal tumors must be taken into account for the decision of primary treatment. Regarding the important locoregional aggressivity of squamous cell carcinomas of the upper aerodigestive tract, these results must be kept in mind when preservation protocols are in question.     

Gene therapy for head and neck cancers

Despite advances in surgery, radiotherapy, and chemotherapy, survival of patients with squamous cell carcinoma of the head and neck has not significantly improved over the past 30 years. Locally recurrent or refractory disease is particularly difficult to treat. Repeat surgical resection and/or radiotherapy are often not possible, and long-term results for salvage chemotherapy are poor. Recent advances in gene therapy have been applied to recurrent squamous cell carcinoma of the head and neck. Many of these techniques are now in clinical trials and have shown some efficacy. This article discusses the techniques employed in gene therapy and summarizes the ongoing protocols that are currently being evaluated in clinical trials.     

侵犯上呼吸消化道的高分化甲状腺癌的治疗

目的：探讨侵犯上呼吸消化道的高分化甲状腺癌的治疗方式。方法：回顾性分析62例侵犯上呼吸消化道的高分化甲状腺癌的治疗方法。全组均行手术治疗,术式以肿瘤削除术为主,17例患者术后行放射性碘治疗,3例行术后放疗。全部病例随访2～15年。结果：肿瘤局限性侵犯患者,手术削除干净无残留者5年局部控制率达100．0％(17／17);肿瘤广泛侵犯突入腔内而行扩大切除者为87．5％(7／8);局限性侵犯、手术削除不干净有残留者为55．6％(5／9)。姑息性切除疗效最差。17例少量肿瘤残留者术后行放射性碘治疗,其5年局部控制率与未作此治疗者,差异有显著性。结论：对于侵犯上呼吸消化道的高分化甲状腺癌,应根据具体情况选择合适的术式;对有少量肿瘤残留者术后应辅以同位素治疗,病程较晚期者宜行术后放疗。     

The role of salvage surgery in patients with recurrent squamous cell carcinoma of the oropharynx

BACKGROUND:

The objective of this study was to comprehensively review overall survival, functional outcomes, and prognostic factors in patients who underwent salvage surgery for locally recurrent squamous cell carcinoma of the oropharynx (SCCOP) after initial radiotherapy.

METHODS:

The authors retrospectively reviewed 1681 consecutive patients who completed definitive therapy for primary SCCOP and identified 168 patients with locally recurrent SCCOP who underwent salvage surgery (41 patients), reirradiation or brachytherapy (18 patients), palliative chemotherapy (70 patients), or supportive care (39 patients).

RESULTS:

Twenty‐six of 39 patients (67%) developed a second recurrence after salvage surgery. The 3‐year overall survival rate for patients who underwent salvage surgery or received reirradiation, palliative chemotherapy, or supportive care were 48.7%, 31.6%, 3.7%, and 5.1%, respectively. For patients who underwent salvage surgery, older age (P = .03), the absence of a disease‐free interval (P < .01), and advanced recurrent tumor stage (P = .07) were associated with lower overall survival. Patients with recurrent neck disease (P = .01) and positive surgical margins (P = .04) had higher rates of recurrence after salvage surgery. Postoperative complications occurred in 19 patients (46%), and there were no perioperative deaths. Functionally, 71% of patients demonstrated ≥80% speech intelligibility, 68% were able to tolerate some oral intake, and 87% who required a tracheotomy subsequently were decannulated.

CONCLUSIONS:

Age, disease‐free interval, recurrent tumor stage, recurrent neck disease, and surgical margin status influenced overall survival or recurrence rate after salvage surgery for recurrent SCCOP. Although most patients had good functional outcomes, only a select group of patients with recurrent SCCOP achieved long‐term survival after salvage surgery. Cancer 2009. © 2009 American Cancer Society.     

Management of the N0 neck--reference or preference

For patients with squamous cell carcinoma of the upper aerodigestive tract, appropriate management of the regional lymph nodes is an important and often controversial issue that has significant influence on survival. Over the years radical treatment either by surgery or radiotherapy contributed to improvement in prognosis. Recently, a more conservative approach has achieved a similar level of cancer control with less morbidity. This review considers the issues of selection of patients for treatment of the neck, choice of modality and extent of therapy, treatment of the contralateral neck, management of recurrence and influence of the site and status of the primary lesion.     

Glottic carcinoma. The roles of surgery and irradiation

The treatment of 336 patients with squamous cell carcinoma of the glottic larynx seen at the University of Virginia Medical Center from 1960 through 1977 was reviewed. Two hundred eighty-five patients form the basis of this report. Patients were grouped by stage and by other prognostic factors. Five-year actuarial survival, recurrences, salvage therapy, complications, second primaries, and incidence in patients younger than 45-years-old were examined. The actuarial 5-year survivals are Stage I, 96%; Stage II, 88%; Stage III, 65%; and Stage IV, 57%. Early glottic carcinoma responded equally well to radiation therapy or surgery, and mortality from intercurrent disease was more common than death from glottic carcinoma. Anterior commissure involvement was not found to significantly decrease prognosis in Stage I disease. Within Stage II, patients with impaired true cord mobility had a significantly decreased survival, 71%, versus 93% for Stage II carcinoma with mobile cords. Surgery was superior to irradiation when cord mobility was impaired or fixed. Surgical salvage was successful in 70% of cases when the cords were originally mobile but 11% when cord motion had been impaired or fixed. Patients younger than age 45 years presented with more advanced disease, but by stage, treatment response did not differ from the remaining older group. Based on this review and from data reported in the literature, the authors recommend curative radiation therapy in patients with glottic carcinoma where the vocal cords are fully mobile. When cord mobility is impaired or fixed, the inclusion of surgery in the initial management results increased survival over irradiation alone. Recognizing that glottic carcinoma is often part of a multisystem disease, individualization of treatment is especially important in these advanced tumors.     

Carcinogenesis of head and neck cancer and the role of chemoprevention in its reversal

Head and neck cancer is an important public health problem worldwide, accounting for approximately 40,400 new cancer cases and 12,300 cancer deaths annually in the US. Although early-stage disease is often curable with surgery or radiotherapy, the majority of patients present with advanced disease in which despite advances in combined modality therapy the outcomes have not dramatically improved. Furthermore, patients cured of their initial early-stage head and neck squamous cell carcinoma are at high risk for development of second primary tumors, which pose the main threat to survival. An alternative approach in reducing the incidence and thus mortality associated with these cancers is chemoprevention, the use of agents to reverse, halt, or delay carcinogenesis. The carcinogenesis process in head and neck cancer results from a dysregulation of cellular proliferation, differentiation, and cell death resulting from field-wide exposure of the upper aerodigestive tract to tobacco smoking. Newly acquired knowledge in the field of tumor biology and of the genetic changes underlying carcinogenesis through the use of new molecular technology represents the basis on which chemoprevention efforts should be based.     

The role of radiation therapy in squamous cell carcinoma of the upper aerodigestive tract with positive surgical margins

One hundred four patients with squamous cell carcinoma of the upper aerodigestive tract and with histologically positive surgical margins were evaluated for this historically controlled study to determine the efficacy of postoperative radiation therapy. Positive margins were defined as the presence of one or more of the following: carcinoma in situ, tumor within 0.5 cm from the surgical margins, microscopic disease, or dysplasia. Patients received either surgery alone (44 cases) or surgery plus postoperative radiation therapy (60 cases) and were followed for a minimum of 2 years. Treatment strategies, stage by stage, were similar for all patients. Surgery varied from simple excision in T1 to composite resection and/or laryngopharyngectomy with radical neck dissection in advanced cases. Radiation therapy was given postoperatively with doses ranging from 4,500 to 7,500 cGy. The overall 2-year survival rate with no evidence of disease (NED) was consistently higher in the surgery plus radiation therapy group. Furthermore, when the subgroup of patients who had dysplasia at the surgical margins was excluded from the analysis, the 2-year NED survival rate difference became statistically significant (p = 0.05). This outcome favored combined therapy (36 of 58 patients) over surgery alone (13 of 32 patients). This favorable result was obtained despite the high percentage of T3-T4 stages (79 vs. 21%) and clinically positive lymph nodes (83 vs. 17%) in patients who had received postoperative radiation therapy. The significance of dysplasia at the surgical margins and the impact of radiation therapy on the tumor and nodal control in this group of patients needs further clarification.     

Salvage surgery as the primary treatment for recurrent oral squamous cell carcinoma

The choice of salvage modalities of recurrent squamous cell carcinoma (SCC) of the oral cavity remains controversial. We investigated the feasibility of the surgical salvage treatment as a primary option. From 1989 to 1999, curative intended surgery was performed on 191 patients with SCC of the oral cavity at National Cheng Kung University Hospital in Taiwan. These patients were divided into fresh group and salvage group. Survival and complication rates were analyzed for both groups. Patients with early and late recurrent stage had 60 and 38% 5-year absolute survival after salvage surgery. The overall complication rate was higher in the salvage group (60.7 vs 30.4%, P<0.0001), but the major complication rate was not significantly different between these groups (P=0.121). Surgery achieves an acceptable survival in recurrent oral SCC without increasing the major complication rate. Thus surgery is concluded to be a reliable and feasible treatment of choice.     

Recurrences in the soft tissues of the neck after surgery or radiotherapy plus surgery on regional lymph nodes in patients bearing carcinomas of the head and neck

A series of 45 recurrences in the soft tissues of the neck following lymph node dissection in 497 patients bearing carcinoma of the upper aerodigestive passages is reported. Only 22 cases that presented perilymph node metastases and/or in which there were reasons to indicate insufficient surgical radicality had been subjected to radiotherapy after surgical lymph node dissection; the other 23 cases had not been subjected to radiotherapy because the aforementioned premises had been lacking. All the recurrences therefore occurred in patients with clinically and histologically ascertained metastatic lymph nodes. The presence of perilymph node metastases and the judgment of surgical radicality was thus found insufficient criteria to plan future complementary postoperative radiotherapy. However, even in those cases in which postoperative radiotherapy was performed, there was a rather high incidence of recurrences, as high as 64.7% in patients with carcinoma of the tongue. Our data indicate the opportunity of a clinical trial with preoperative radiation therapy in patients with clinically evident lymph node metastases. Thirty-six of these recurrences were situated in the upper parts of the cervical region. The prognosis is very poor in such cases, so much so that only 2 of our series were disease free at 3 years after the treatment.     

新辅助治疗联合手术治疗后复发食管鳞癌再程治疗的预后分析

目的 分析新辅助治疗联合手术治疗后复发的食管鳞癌再程治疗疗效及影响预后因素。方法 回顾分析2011-2015年间新辅助治疗+手术治疗后失败的152例胸段食管鳞癌治疗失败后总生存(OS)及不同挽救治疗的疗效及预后因素。Kaplan-Meier法计算OS,Cox模型多因素预后分析。结果 术后首次复发的中位间隔时间为10.6(2.0~69.1)个月。复发后的中位OS期为8.0(0.8~43.3)个月。全组患者复发后的1、2、3年OS率分别为36.0%、15.1%、5.2%。单纯局部区域复发、单纯远处转移、局部区域复发合并远处转移患者进展后中位OS期分别为11.3(1.8~43.3)、6.7(1.2~28.6)、5.1(0.8~22.9)个月。多因素分析显示新辅助化疗、ypTNM分期、复发后综合治疗、局部区域复发与复发食管鳞癌OS相关(P=0.009、0.012、0.000、0.026)。结论 新辅助治疗模式、ypTNM分期、复发模式及复发后治疗模式是是影响新辅助治疗+手术治疗后复发食管鳞癌的预后因素。新辅助治疗后复发食管鳞癌总体预后不佳,复发后应根据复发位置、新辅助治疗模式、患者体力状态等因素采用综合治疗模式以使患者取得最大挽救治疗获益。     

新辅助治疗联合手术治疗后复发食管鳞癌再程治疗的预后分析

目的 分析新辅助治疗联合手术治疗后复发的食管鳞癌再程治疗疗效及影响预后因素。方法 回顾分析2011-2015年间新辅助治疗+手术治疗后失败的152例胸段食管鳞癌治疗失败后总生存(OS)及不同挽救治疗的疗效及预后因素。Kaplan-Meier法计算OS,Cox模型多因素预后分析。结果 术后首次复发的中位间隔时间为10.6(2.0~69.1)个月。复发后的中位OS期为8.0(0.8~43.3)个月。全组患者复发后的1、2、3年OS率分别为36.0%、15.1%、5.2%。单纯局部区域复发、单纯远处转移、局部区域复发合并远处转移患者进展后中位OS期分别为11.3(1.8~43.3)、6.7(1.2~28.6)、5.1(0.8~22.9)个月。多因素分析显示新辅助化疗、ypTNM分期、复发后综合治疗、局部区域复发与复发食管鳞癌OS相关(P=0.009、0.012、0.000、0.026)。结论 新辅助治疗模式、ypTNM分期、复发模式及复发后治疗模式是是影响新辅助治疗+手术治疗后复发食管鳞癌的预后因素。新辅助治疗后复发食管鳞癌总体预后不佳,复发后应根据复发位置、新辅助治疗模式、患者体力状态等因素采用综合治疗模式以使患者取得最大挽救治疗获益。     

Management of locally invasive well-differentiated thyroid cancer

Thyroid carcinoma invasion of the aerodigestive tract and recurrent laryngeal nerve (RLN) are important factors with increase in morbidity and mortality. Primary treatment is surgery; the decision about the extent of surgery is difficult, because preserving function is as essential as removal of the tumor. This article discusses the literature relating to the assessment of disease, surgical management, and adjuvant therapy for invasive thyroid cancer of the aerodigestive tract and RLN and makes suggestions based on the authors' experience.     

Recurrence patterns in squamous cell carcinoma of the oral cavity, pharynx, and larynx

The purpose of this review is to document patterns of failure with the existing modalities of therapy in carcinomas of the upper aerodigestive tract. Most attention is given to regional failure, which is separately divided into primary site and metastatic cervical adenopathy. Survival, stage of the lesion, conversion of the clinically negative neck, and salvage of treatment failure is discussed. Either with surgery, radiations or combination, the commonest regional failure still remains in the primary site. Of additional importance is the unexpectedly poor salvage rate of previous treatment failures (16%). Histologically involved lymph nodes appears to portend a poor prognosis with a high failure rate seen not only in the neck but also in the primary site with or without distant metastases. Nodal involvement indicates mostly the aggressive biological nature of the primary lesion. The most common failing by authors, whose reports had to be excluded from this review, was a preoccupation with survival statistics and a general inattention paid to documenting the specific failure site.     

Subsequent upper aerodigestive malignancies following treatment of esophageal cancer

One hundred ninety-eight patients received radiation therapy for carcinoma of the esophagus. Eight patients subsequently developed at least one other epidermoid carcinoma within the upper aerodigestive tract. Analysis by life-table method suggests a steadily increasing risk for second malignancies as survival lengthens. Implications with regard to the treatment and management of patients with squamous cell carcinoma of the esophagus are discussed and the relevant literature is reviewed.     

Re-irradiation for head and neck squamous cell carcinoma

Introduction

Local recurrences after curative treatment have a potential for cure with salvage surgery or with re-irradiation.